Objective: To determine the efficacy and tolerability of a long-acting intramuscular formulation of Nalmefene (Nalmefene Consta 393.1 mg) for the treatment of opioid-dependent patients. Design, Setting, and Participan...Objective: To determine the efficacy and tolerability of a long-acting intramuscular formulation of Nalmefene (Nalmefene Consta 393.1 mg) for the treatment of opioid-dependent patients. Design, Setting, and Participants: A 12 weeks, open-label, randomised controlled trial conducted between June 2009-July 2011, at 14 Hospital-based drug clinics, in the 12 countries. Participants were 18 years or older, had Diagnostic and Statistical Manual of Mental Disorders-5 opioid use disorder. Of the 3200 individuals screened, 3000 (93.7%) adults were randomized 1500 participants to receive injections of Long-acting depot formulations ofNalmefene (Nalmefene Consta 393.1 mg) given intramuscularly once in 12 weeks and 1500participants to receive extended-release Naltrexone (Vivitrol 380 mg), administered intramuscularly every fourth week for 12 weeks. Main Outcomes and Measures: The primary endpoints (protocol) were: Confirmed Opioid abstinence (percentage i.e. the number of patients who achieved complete abstinence during week 12). Confirmed abstinence or “opioid-free” was defined as a negative urine drug test for opioids and no self-reported opioid use. Weeks 1 - 4 were omitted from this endpoint to allow for stabilization of abstinence. Secondary end points included a number of days in treatment, treatment retention and craving. The study also investigated, on 275 participants, degree and time course of mu-opioid receptor occupancy following single doses of Nalmefene extended-release injection (Nalmefene Consta 393.1 mg) as well as the plasma concentration of Nalmefene and Nalmefene-3-O-glucuronide. Safety was assessed by adverse event reporting. Results: Of 3000 participants, mean (SD) age was 27.1 (±4.8) years and 831 (27.7%) were women. 1500 individuals were randomized to receive injections of Long-acting depot formulations of Nalmefene (Nalmefene Consta 393.1 mg) and 1500 to receive injections of extended-release Naltrexone (Vivitrol 380 mg);2088 participants (69.6.0%) completed the trial. Primary endpoints: Confirmed Opioid Abstinence: Complete abstinence was sustained by 86% (n = 1290) of Nalmefene patients (patients treated with Nalmefene Consta 393.1 mg, long-acting depot formulations) compared with 43% (n = 645) of patients treated with extended-release Naltrexone 380 mg (Vivitrol), during weeks 5 - 12 (χ2 = 672.34, P Secondary Endpoint: Craving: A statistically and clinically significant reduction in opioid craving was observed with Nalmefene (Nalmefene Consta 393.1 mg, long-acting depot formulations) vs. Naltrexone (extended-release Naltrexone, Vivitrol 380 mg) by week 4 (P =0.0048), which persisted every week through 12 (P < 0.0001). Patients given Nalmefene (Nalmefene Consta 393.1 mg, long-acting depot formulations) had a 75% decrease in craving from baseline to week 12. Patients given a Naltrexone (extended-release Naltrexone, Vivitrol 380 mg) had a 3% increase in craving from baseline to week 12 (Mean change in self-reporting craving). Secondary Endpoint: Treatment Retention: Long-acting intramuscular formulation of Nalmefene (Nalmefene Consta 393.1 mg) helped significantly more patients complete 12 weeks treatment (n = 1245, 83%) compared with extended-release Naltrexone (Vivitrol 380 mg) (n = 570, 38%) (χ2 = 635.53, P < 0.0001). Patients on long-acting intramuscular formulation of Nalmefene (Nalmefene Consta 393.1 mg) had longer treatment retention than patients on extended-release Naltrexone (Vivitrol 380 mg). Concentrations of Nalmefene and Nalmefene-3-O-Glucuronide in Plasma: Analyses were made of 275 study sample. There was no statistically significant difference for plasma nalmefene concentrations between days 2 and 84 (p = 0.416). The plasma concentration of Nalmefene were 20.3 and 28.5 ng/ml and concentrations of nalmefene-3-O-glucuronide were 2.1 and 4.1 ng/ml, respectively. Plasma levels of Nalmefene remained above 20 ng/ml for approximately 12 weeks after administration of Nalmefene, long-acting depot formulations (Nalmefene Consta 393.1 mg). PET Assessments: Very high mu-opioid receptor occupancy by Nalmefene was detected 1 day after treatments at which time point the occupancy was 100.0% after Nalmefene injection (Nalmefene Consta 393.1 mg). Nalmefene Consta 393.1 mg injection (long-acting intramuscular formulation of Nalmefene) led to a very high occupancy ofmu-opioid receptors in all brain areas examined;the thalamus, caudate nucleus, and frontal cortex. Depending on the brain area mu-opioid receptor occupancy varied between 83.0% and 85.8% 84 days after dosing. Adverse Reactions: Adverse events were similar in opioid-dependent patients treated with long-acting intramuscular formulation of Nalmefene (Nalmefene Consta 393.1 mg) vs. patients treated with extended-release Naltrexone (Vivitrol 380 mg). Conclusions and Relevance: Long-acting depot formulations of Nalmefene (Nalmefene Consta 393.1 mg) was more effective then extended-release Naltrexone (Vivitrol 380 mg) in maintaining short-term abstinence from heroin and should be considered as a treatment option for opioid-dependent individuals.展开更多
Objective: To determine the efficacy and tolerability of a long-acting intramuscular formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) for treatment of cocaine-dependent patients. Design, Setting, and Participant...Objective: To determine the efficacy and tolerability of a long-acting intramuscular formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) for treatment of cocaine-dependent patients. Design, Setting, and Participants: A 12-week, A multicenter, randomized, placebo-controlled trial conducted between June 2009-July 2011, at 17 Hospital-based drug clinics, in the 15 countries. Participants were 18 years or older, had Diagnostic and Statistical Manual of Mental Disorders-5 cocaine use disorder. Of the 2800 patients who were assessed between March 10, 2009 to August 10, 2010, 2600 (93%) were eligible and willing to take part in the trial and were enrolled: 1300 were randomly assigned to receive injections of Long-acting depot formulations of Vanoxerine (Vanoxerine Consta 394.2 mg) given intramuscularly once in 12 weeks and 1300 to receive Placebo injections, given intramuscularly once in 12 weeks. Only 100 of 2800 patients (3.6%) did not meet the inclusion criteria. Main Outcomes and Measures: The primary endpoints (protocol) were: Confirmed Cocaine abstinence (percentage i.e. the number of patients who achieved complete abstinence during 12 weeks). Confirmed abstinence or “cocaine-free” was defined as a negative urine drug test for cocaines and no self-reported cocaine use. Secondary end points included a number of days in treatment, treatment retention and craving. The study also investigated, on 275 participants, degree and time course of Central Dopamine transporter receptor occupancy following single doses of long-acting intramuscular formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) as well as the plasma concentration of Vanoxerine and 17-hydroxyl Vanoxerine. Safety was assessed by adverse event reporting. Results: Of 2600 participants, mean (SD) age was 28.5 (±5.5) years and 598 (23%) were women. 1300 individuals were randomized to receive injections of Long-acting depot formulations of Vanoxerine (Vanoxerine Consta 394.2 mg) and 1300 to receive injections of Placebo. 1417 participants (54.5.0%) completed the trial. Primary Endpoints: Confirmed Cocaine Abstinence: Complete abstinence was sustained by 72% (n = 936) of Vanoxerine patients (patients treated with Vanoxerine Consta 394.2 mg, long-acting depot formulations) compared with 37% (n = 481) of patients treated with Placebo, during weeks 5 - 12. The difference was significant as evaluated using a Chi-square test (χ2 = 672.34, P < 0.0001). Secondary Endpoint: Craving: A statistically and clinically significant reduction in cocaine craving was observed with Vanoxerine (Vanoxerine Consta 394.2 mg, long-acting depot formulations) vs. Placeboby week 4 (P = 0.0048), which persisted every week through 12 (P < 0.0001). Patients given Vanoxerine (Vanoxerine Consta 394.2 mg, long-acting depot formulations) had a 87% decrease in craving from baseline to 12th week. Patients given a Placebo had a 2% increase in craving from baseline to 12th week. Secondary Endpoint: Treatment Retention: Long-acting intramuscular formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) helped significantly more patients complete 12 weeks treatment (n = 936, 72%) compared with Placebo (n = 481, 37%) (χ2 = 635.53, P < 0.0001). Patients on the long-acting intramuscular formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) had longer treatment retention than patients on Placebo. Concentrations of Vanoxerine and 17-Hydroxyl Vanoxerinein Plasma: Analyses were made of 275 study samples. There was no statistically significant difference for plasma Vanoxerine concentrations between days 2 and 84 (p = 0.416). The plasma concentration of Vanoxerine were 70.4 and 94.3 ng/ml and concentrations of 17-hydroxyl Vanoxerine were 10.5 and 13.2 ng/ml, respectively. Plasma levels of Vanoxerine remained above 70 ng/ml for approximately 12 weeks after administration of Vanoxerine, long-acting depot formulations (Vanoxerine Consta 394.2 mg). PET Assessments: Very high central dopamine transporter receptor occupancy by Vanoxerine was detected 1 day after treatments, at which time point the occupancy was 100.0% after Vanoxerine injection (Vanoxerine Consta 394.2 mg). At days 7, 28, 56 and 84 post-Vanoxerine Consta 394.2 mg administration, occupancies were 95% to 79%. Vanoxerine Consta 394.2 mg injection (long-acting intramuscular formulation of Vanoxerine) led to very high occupancy of Central Dopamine transporter receptors in all brain areas examined;nucleus accumbens, caudate nucleus and putamen. Depending on the brain area Central Dopamine transporter receptor occupancy varied between 95.0% and 79% at days 7, 28, 56 and 84 after dosing. High Vanoxerine occupancy (77%) persisted at 12 weeks after the dosings. Adverse Reactions: Adverse events were similar in cocaine-dependent patients treated with the long-acting intramuscular formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) vs. patients treated with Placebo. Conclusions and Relevance: Long-acting depot formulations of Vanoxerine (Vanoxerine Consta 394.2 mg) were more effective than Placebo injection in maintaining short-term abstinence from cocaine and should be considered as a treatment option for cocaine-dependent individuals.展开更多
Risperidone long-acting injectable (RLAI) is approved for the treatment of schizophrenia in many countries. The suggested site is the gluteal muscle with a needle length of two inches (50 mm) in Japan, which is longer...Risperidone long-acting injectable (RLAI) is approved for the treatment of schizophrenia in many countries. The suggested site is the gluteal muscle with a needle length of two inches (50 mm) in Japan, which is longer than the ordinarily used needle for intramuscular injections. The aim of this study was to determine the optimal needle insertion length for accurate delivery of RLAI procedure among subjects who have normal body mass index (BMI: 18 to 25) and high BMI (>25). Thirty-seven patients with schizophrenia were administered RLAI intramuscularly into the dorsogluteal muscle. The standard procedure required inserting 80% of the two inch needle. By using data collected by ultrasonography, the findings confirmed that the median needle insertion lengths for subjects with normal and high BMI were 39.0 and 45.5 mm, respectively. To deliver RLAI effectively and safely, the authors strongly recommend that a specialized needle be used that is “marked” at the 40 mm point from the tip of the needle to the base. In this way regardless of subcutaneous fat content, the RLAI can be safely delivered into the muscle without causing untoward or side effects.展开更多
BACKGROUND Women with a history of serious psychotic disorders are at increased risk of disease relapse during pregnancy.Long-acting injectable(LAI)antipsychotics have been widely used to improve adherence and prevent...BACKGROUND Women with a history of serious psychotic disorders are at increased risk of disease relapse during pregnancy.Long-acting injectable(LAI)antipsychotics have been widely used to improve adherence and prevent relapse in patients with various severe psychotic disorders,but there is a lack of high-quality data from previous research on the safety of LAI antipsychotics during pregnancy.AIM To summarize relevant data on maternal,pregnancy,neonatal,and developmental outcomes from published cases of LAI antipsychotic use in pregnancy.METHODS A literature search was performed through November 11,2023,using three online databases:PubMed/MEDLINE,Scopus,and Web of Science.Case reports or case series that reported information about the outcomes of pregnancy in women who used LAI antipsychotics at any point in pregnancy,with available full texts,were included.Descriptive statistics,narrative summation,and tabulation of the extracted data were performed.RESULTS A total of 19 publications satisfied the inclusion criteria:3 case series,15 case reports,and 1 conference abstract.They reported the outcomes of LAI antipsychotic use in 74 women and 77 pregnancies.The use of secondgeneration LAI antipsychotics was reported in the majority(n=47;61.0%)of pregnancies.First-generation LAI antipsychotics were administered during 30 pregnancies(39.0%).Most of the women(approximately 64%)had either satisfactory control of symptoms or no information about relapse,while approximately 12%of them had developed gestational diabetes mellitus.A minority of cases reported adverse outcomes such as stillbirth,spontaneous abortion,preterm birth,low birth weight,congenital anomalies,and neurological manifestations in newborns.However,there were no reports of negative long-term developmental outcomes.CONCLUSION Currently available data seem reassuring,but further well-designed studies are required to properly evaluate the risks and benefits of LAI antipsychotic use during pregnancy.展开更多
In some cases, if the insertion depth is shallower than expected, intramuscular (IM) injection of risperidone long-acting injectable (RLAI) may not penetrate the muscle fascia. However, if needle insertion depth is de...In some cases, if the insertion depth is shallower than expected, intramuscular (IM) injection of risperidone long-acting injectable (RLAI) may not penetrate the muscle fascia. However, if needle insertion depth is deeper than anticipated, needle penetration may cause damage to nerves, arteries and veins. Few clinical studies were done to evaluate the depth of needle length insertion reaching the intended gluteal muscle. The aim of this study was to evaluate the suitable depth of injecting RLAI. Twenty-six patients with schizophrenia were treated with RLAI, and randomly divided into two groups: 50 mm needle inserted group (Group-D, deep insertion, n = 13) and 20 mm needle insertion group (Group-S, shallow insertion, n = 13). For Group-S, the needle length was marked with a spacer at exactly 20 mm. Injections were performed by the psychiatrist or nurse, alternating between the two gluteal sites by double-cross method every two weeks. Clinical psychotic symptoms and injection site reactions were recorded throughout the study period. Experienced psychologists who were blinded from the needle-length experimental variable evaluated patients’ psychotic symptoms using the Positive and Negative Syndrome Scale (PANSS) every two weeks. The plasma 9-hydroxyrisperidone (9-OH-RIS) concentrations were measured every two weeks;comparison data were determined on the 8th week and the 14th week. No significant difference was observed in 9-OH-RIS concentrations, psychotic symptoms, injection site skin reactions of subjects in both groups. However, in Group-D, injection site adverse reactions were confirmed in two subjects (15%). In Group-S, injection site reactions were confirmed in six subjects (46%). Although effective 9-OH-RIS concentrations were obtained with the insertion using both depth, it was concluded that the 50 mm insertion length was more suitable for dorsogluteal IM injections in adult patients with schizophrenia as demonstrated by the incidence of local adverse skin reactions.展开更多
The objectives of e-STAR Romania (NCT00283517) were to collect clinical outcome data of Romania schizophrenia or schizo-affective disorder patients;prospectively to assess the reasons of treatment initiation, medicati...The objectives of e-STAR Romania (NCT00283517) were to collect clinical outcome data of Romania schizophrenia or schizo-affective disorder patients;prospectively to assess the reasons of treatment initiation, medication usage patterns;to document (long-term) clinical efficacy;and to collect safety data, as well as recording 2-year corresponding retrospective data. In total, 378 eligible subjects were enrolled who were initiated either on risperidone long-acting injectable (RLAI) (290) or on an oral antipsychotic (OA) (88) at baseline as required by the local Summary of the Product Characteristics. Data were collected from per patient both retrospectively and prospectively over a 24-month period at 3-month intervals after starting treatment. The results indicated that subjects suffering from schizophrenia or schizo-affective disorder initiated on RLAI were less likely to be hospitalized within the first 24 months after the initiation of treatment. Moreover, subjects treated with RLAI experienced significant improvements in their illness severity and functioning. Discontinuation rates for RLAI were low and doses were stable throughout the 24 months following the initiation of treatment. In addition, the necessity for supplementary concomitant medication was reduced. Adverse events were reported in 20.3% (RLAI) and 11.4% (OA) of the subjects. In general, patients initiated on RLAI and OA at baseline both clinically improved on all assessed parameters but a larger improvement was observed for patients on RLAI. Incidences of reported AEs during the use of RLAI in a naturalistic setting are comparable with those described in clinical studies;however, the incidence of extrapyramidal signs and weight gain was lower than expected.展开更多
In the present study,we aimed to determine the pharmacokinetics(PK),pharmacodynamics(PD),adverse events(AEs),and their relationships in Chinese patients with schizophrenia after a single dose of long-acting risperidon...In the present study,we aimed to determine the pharmacokinetics(PK),pharmacodynamics(PD),adverse events(AEs),and their relationships in Chinese patients with schizophrenia after a single dose of long-acting risperidone.Schizophrenic patients(six females and seven males)were enrolled in this study.Serial blood samples were collected after drug administration during 63 d,and the drug concentrations were analyzed by LC-MS/MS.Safety and tolerance were evaluated by monitoring the AEs,changes in clinical laboratory results,12-lead ECG,vital signs,physical examination,and injection-site reactions.The extrapyramidal symptoms were evaluated using the ESRS.Efficacy was evaluated by the PANSS and BPRS.Twelve out of the 13 participants completed the trial.There were few clinically meaningful changes in mean clinical laboratory values,vital signs,or ECG parameters,except for the prolactin level and body weight.There were no serious AEs,and those observed were reversible.Significant clinical improvements in PANSS and PANSS-derived BPRS total scores were observed.The mean(standard deviation,coefficient of variation)values for these PK parameters were as follows:C_(max),8.954(8.059,90.0%)ng/mL;area under the curve AUC_(0-t),2453(1156,47.1%)ng·h/mL;AUC_(0-∞),2472(1160,46.9%)ng·h/mL;t_(max),830.0(min:744.0,max:984.0,11.8%)h;and t_(1/2),68.56(10.77,15.7%)h.The PK characteristics of long-acting risperidone showed a high level of inter-individual variation,while there were no clear correlations between PK,efficacy and AEs among the patients in the present study.展开更多
Despite advances in treatment of chronic arthritis,there is still a strong need for the development of long-acting formulations that can enable local and sustained drug release at the inflamed tissues.In this work,we ...Despite advances in treatment of chronic arthritis,there is still a strong need for the development of long-acting formulations that can enable local and sustained drug release at the inflamed tissues.In this work,we fabricated microcrystals of an acid-sensitive stearoxyl-ketal-dexamethasone prodrug for treatment of arthritis.Microcrystals of the prodrug with two sizes were successfully engineered and showed pH-dependent hydrolysis kinetics in vitro.In a collagen-induced arthritis rat model,we evaluated the influence of particle size and injection dose on anti-inflammatory effect after intra-articular injection.Such prodrug demonstrated long-acting anti-arthritis effects with good safety.Our results indicate ketal-based prodrugs are promising for the development of long-acting injectables and may stimulate the development of new treatments for chronic diseases.展开更多
For the quantitative determination of Fulvestrant, Benzyl alcohol, and Benzyl benzoate in Fulvestrant injection, an original RP-HPLC approach was developed. The gradient method was developed using HPLC and a Phenomene...For the quantitative determination of Fulvestrant, Benzyl alcohol, and Benzyl benzoate in Fulvestrant injection, an original RP-HPLC approach was developed. The gradient method was developed using HPLC and a Phenomenex Luna C8, 150 × 4.6 mm, i.d 3.0 μm particle size column with a gradient programme of mobile phases A and B. With a flow rate of 1.5 mL/minute, injection volume of 10 μL, and column temperature of 35°C, UV wavelength detection at 254 nm for Benzyl alcohol and Benzoyl Benzoate and 280 nm for Fulvestrant, mobile phase-A consists of DI water and mobile phase-B consists of Acetonitrile. The current study describes a single HPLC method for developing a Fulvestrant (Active), Benzyl alcohol (Cosolvent), and Benzyl Benzoate (Cosolvent) assay for Fulvestrant injection. The assay method was determined to be suitable for quantifying three components in the pharmaceutical product and was verified according to ICH guidelines.展开更多
Bupivacaine encapsulated poly(lactidecoglycolide)nanoparticles is a novel formulation of extended-release of bupivacaine in poly(lactidecoglycolide)matrix.We evaluated the efficacy and safety of bupivacaine nanopartic...Bupivacaine encapsulated poly(lactidecoglycolide)nanoparticles is a novel formulation of extended-release of bupivacaine in poly(lactidecoglycolide)matrix.We evaluated the efficacy and safety of bupivacaine nanoparticles in peripheral analgesia via behavior tests,electrophysiological recordings,pharmacokinetic analysis,and pathology staining by employing the models of uninjured rats and mice.Nanoparticles injection increased the pain thresholds of rats and mice for 21 days.展开更多
Affected by reservoir heterogeneity, there is often a serious problem of water channeling in the late stage of water injection oilfield development. Conventional water injection adjustment is difficult to further impr...Affected by reservoir heterogeneity, there is often a serious problem of water channeling in the late stage of water injection oilfield development. Conventional water injection adjustment is difficult to further improve water drive recovery. It is necessary to adopt deep profile control and displacement technology to block water channeling channel and improve water drive efficiency.Based on the analysis of deep profile control and flooding mechanism, this paper analyzes the composition, technical indexes and adaptive conditions of seven types of profile control and flooding agent formula system, and takes block J as an example to analyze the deep adjustment effect in detail, including profile control and flooding agent system, injection volume and changes of various indexes after profile control and flooding. The effect of increasing oil and controlling water is remarkable, with an efficiency of 36.148 million yuan and an input-output ratio of 1:2.81,To achieve the purpose of cost reduction and efficiency increase under low oil prices, the achievements and understanding can provide reference experience for peers.展开更多
Background Little information about the current management of patients with thyroid-stimulating hormone （TSH）-secreting pituitary adenomas or about the usefulness of the somatostatin analogue octreotide was containe...Background Little information about the current management of patients with thyroid-stimulating hormone （TSH）-secreting pituitary adenomas or about the usefulness of the somatostatin analogue octreotide was contained in the literature. This study aimed to report the efficacy and safety of the long-acting octreotide formulation in patients with TSH-secreting pituitary adenomas after incomplete surgery and octreotide treatment failure. Methods Fifteen patients with TSH-secreting pituitary adenomas （8 men and 7 women）, who previously underwent incomplete surgical resection and/or adjuvant radiotherapy （n=12） and failure of octreotide treatment （n=15）, followed between 2007 and 2010 in Beijing Tiantan Hospital were included in this study. All patients received 1- to 2-months of the long-acting octreotide formulation treatment after the above combination of treatment. Paired samples t-test was used to analysis the variables. Results After two-month duration of the long-acting octreotide formulation treatment, the mean serum free or unbound thyroxine （FT4） （（16.02±1.72） pmol/L） and free triiodothyronine （FT3） （（2.87±0.43） pmol/L） levels of 15 patients significantly decreased compared with those after octreotide-treatment （FT4, （35.36±7.42） pmol/L, P 〈0.001; FT3, （17.85±7.22） pmol/L, P 〈0.001）. Mean TSH levels stayed in the normal range after the long-acting octreotide formulation treatment （（0.72±0.21） mUlL） and were significantly lower than the pretreatment value （（5.27±1.04） mUlL, P 〈0.001）, post-surgery value （（3.37±0.31） mU/L, P 〈0.001） and post-octreotide-treatment value （（4.52±0.41） mU/L, P 〈0.001）. In these patients with TSH-secreting pituitary adenomas there was no evidence of tachyphylaxis. Conclusion The long-acting octreotide formulation may be a useful and safe therapeutic tool to facilitate the medical treatment of TSH-secreting pituitary adenomas in patients who underwent incomplete surgery or need long-term somatostatin analog therapy.展开更多
长效注射剂在治疗慢性疾病方面具有优势,本文对体外评价研究、体内评价研究的相关方法和影响因素进行了梳理,总结了体外释放行为与体内药动学过程的联立和数学建模,综述长效注射剂体内外相关性(in vitro-in vivo correlation,IVIVC)的...长效注射剂在治疗慢性疾病方面具有优势,本文对体外评价研究、体内评价研究的相关方法和影响因素进行了梳理,总结了体外释放行为与体内药动学过程的联立和数学建模,综述长效注射剂体内外相关性(in vitro-in vivo correlation,IVIVC)的分类、实验方法、建立步骤和模型评价方法。由于长效注射剂的多样性,IVIVC研究中不存在通用的体外模型,因此IVIVC研究只能进行逐例建模。综合药物理化性质、剂型设计和药物制剂与给药部位的相互作用对建立长效注射剂IVIVC研究十分重要。展开更多
Medication adherence in patients with schizophrenia is essential for managing symptoms,improving prognosis,and enhancing the quality of life.Despite the importance of adherence,it remains a global challenge.It is infl...Medication adherence in patients with schizophrenia is essential for managing symptoms,improving prognosis,and enhancing the quality of life.Despite the importance of adherence,it remains a global challenge.It is influenced by various factors,including symptom severity(e.g.,excitement and impulse control disorders),attitudes towards medication(e.g.,pharmacophobia),lack of social support,and the communication efficacy of healthcare teams.Regarding assessment tools,self-report questionnaires,such as the Morisky Scale,are common but subject to recall bias.Electronic monitoring devices(e.g.,Medication Event Monitoring System)and pharmacy refill data offer more objective measures of adherence,whereas biomarkers,such as blood drug concentration monitoring,show promise under specific conditions but require further validation.Long-acting injectable antipsychotic medications have shown greater adherence benefits than oral medications.Psychological interventions such as motivational interviewing and mindfulness training,along with multidisciplinary team efforts,including psychiatrists,pharmacists,and psychotherapists,can significantly improve patient outcomes.Future research should integrate innovative drug formulations(e.g.,long-acting,low-side-effect medications),digital health technologies(e.g.,medication reminder apps and wearable devices),and supportive policies(e.g.,community-based free medication services)as well as patient education to enhance disease awareness.However,the ethical and legal dilemmas(e.g.,balancing patient autonomy with involuntary medication)and privacy concerns in technological applications require further exploration.In conclusion,enhancing medication adherence in patients with schizophrenia requires a personalized,multifaceted approach,and collaborative efforts across various sectors to achieve optimal clinical results and social functioning.展开更多
利用14%吡虫啉.敌敌畏注干液剂、4.15%吡虫啉.阿维菌素注干液剂、4.5%吡虫啉注干液剂、10%啶虫脒注干液剂和30%敌畏.氧乐注干液剂等5种药剂进行了树干注射防治危害柳树的光肩星天牛(Anop lophora g labrip enn is(M otschu lsky))试验,...利用14%吡虫啉.敌敌畏注干液剂、4.15%吡虫啉.阿维菌素注干液剂、4.5%吡虫啉注干液剂、10%啶虫脒注干液剂和30%敌畏.氧乐注干液剂等5种药剂进行了树干注射防治危害柳树的光肩星天牛(Anop lophora g labrip enn is(M otschu lsky))试验,并研究了14%吡虫啉.敌敌畏注干液剂田间防治光肩星天牛的使用技术。结果表明,供试的5种注干药剂对光肩星天牛幼虫均有一定的防治作用,其中14%吡虫啉.敌敌畏注干液剂防效最好。14%吡虫啉.敌敌畏注干液剂以1.0 mL/cm树干胸径注药量对天牛幼虫的防效可达90.7%,优于对照药剂30%敌畏.氧乐注干液剂。利用14%吡虫啉.敌敌畏注干液剂林间防治天牛时,当幼虫虫口密度低于1.15头/株时,1年注药1次;虫口密度约为5头/株时,1年注药2次;虫口密度约为12头/株时,两年注药3次,可将虫口密度控制到0.15头/株以下,有效控制天牛的危害。展开更多
文摘Objective: To determine the efficacy and tolerability of a long-acting intramuscular formulation of Nalmefene (Nalmefene Consta 393.1 mg) for the treatment of opioid-dependent patients. Design, Setting, and Participants: A 12 weeks, open-label, randomised controlled trial conducted between June 2009-July 2011, at 14 Hospital-based drug clinics, in the 12 countries. Participants were 18 years or older, had Diagnostic and Statistical Manual of Mental Disorders-5 opioid use disorder. Of the 3200 individuals screened, 3000 (93.7%) adults were randomized 1500 participants to receive injections of Long-acting depot formulations ofNalmefene (Nalmefene Consta 393.1 mg) given intramuscularly once in 12 weeks and 1500participants to receive extended-release Naltrexone (Vivitrol 380 mg), administered intramuscularly every fourth week for 12 weeks. Main Outcomes and Measures: The primary endpoints (protocol) were: Confirmed Opioid abstinence (percentage i.e. the number of patients who achieved complete abstinence during week 12). Confirmed abstinence or “opioid-free” was defined as a negative urine drug test for opioids and no self-reported opioid use. Weeks 1 - 4 were omitted from this endpoint to allow for stabilization of abstinence. Secondary end points included a number of days in treatment, treatment retention and craving. The study also investigated, on 275 participants, degree and time course of mu-opioid receptor occupancy following single doses of Nalmefene extended-release injection (Nalmefene Consta 393.1 mg) as well as the plasma concentration of Nalmefene and Nalmefene-3-O-glucuronide. Safety was assessed by adverse event reporting. Results: Of 3000 participants, mean (SD) age was 27.1 (±4.8) years and 831 (27.7%) were women. 1500 individuals were randomized to receive injections of Long-acting depot formulations of Nalmefene (Nalmefene Consta 393.1 mg) and 1500 to receive injections of extended-release Naltrexone (Vivitrol 380 mg);2088 participants (69.6.0%) completed the trial. Primary endpoints: Confirmed Opioid Abstinence: Complete abstinence was sustained by 86% (n = 1290) of Nalmefene patients (patients treated with Nalmefene Consta 393.1 mg, long-acting depot formulations) compared with 43% (n = 645) of patients treated with extended-release Naltrexone 380 mg (Vivitrol), during weeks 5 - 12 (χ2 = 672.34, P Secondary Endpoint: Craving: A statistically and clinically significant reduction in opioid craving was observed with Nalmefene (Nalmefene Consta 393.1 mg, long-acting depot formulations) vs. Naltrexone (extended-release Naltrexone, Vivitrol 380 mg) by week 4 (P =0.0048), which persisted every week through 12 (P < 0.0001). Patients given Nalmefene (Nalmefene Consta 393.1 mg, long-acting depot formulations) had a 75% decrease in craving from baseline to week 12. Patients given a Naltrexone (extended-release Naltrexone, Vivitrol 380 mg) had a 3% increase in craving from baseline to week 12 (Mean change in self-reporting craving). Secondary Endpoint: Treatment Retention: Long-acting intramuscular formulation of Nalmefene (Nalmefene Consta 393.1 mg) helped significantly more patients complete 12 weeks treatment (n = 1245, 83%) compared with extended-release Naltrexone (Vivitrol 380 mg) (n = 570, 38%) (χ2 = 635.53, P < 0.0001). Patients on long-acting intramuscular formulation of Nalmefene (Nalmefene Consta 393.1 mg) had longer treatment retention than patients on extended-release Naltrexone (Vivitrol 380 mg). Concentrations of Nalmefene and Nalmefene-3-O-Glucuronide in Plasma: Analyses were made of 275 study sample. There was no statistically significant difference for plasma nalmefene concentrations between days 2 and 84 (p = 0.416). The plasma concentration of Nalmefene were 20.3 and 28.5 ng/ml and concentrations of nalmefene-3-O-glucuronide were 2.1 and 4.1 ng/ml, respectively. Plasma levels of Nalmefene remained above 20 ng/ml for approximately 12 weeks after administration of Nalmefene, long-acting depot formulations (Nalmefene Consta 393.1 mg). PET Assessments: Very high mu-opioid receptor occupancy by Nalmefene was detected 1 day after treatments at which time point the occupancy was 100.0% after Nalmefene injection (Nalmefene Consta 393.1 mg). Nalmefene Consta 393.1 mg injection (long-acting intramuscular formulation of Nalmefene) led to a very high occupancy ofmu-opioid receptors in all brain areas examined;the thalamus, caudate nucleus, and frontal cortex. Depending on the brain area mu-opioid receptor occupancy varied between 83.0% and 85.8% 84 days after dosing. Adverse Reactions: Adverse events were similar in opioid-dependent patients treated with long-acting intramuscular formulation of Nalmefene (Nalmefene Consta 393.1 mg) vs. patients treated with extended-release Naltrexone (Vivitrol 380 mg). Conclusions and Relevance: Long-acting depot formulations of Nalmefene (Nalmefene Consta 393.1 mg) was more effective then extended-release Naltrexone (Vivitrol 380 mg) in maintaining short-term abstinence from heroin and should be considered as a treatment option for opioid-dependent individuals.
文摘Objective: To determine the efficacy and tolerability of a long-acting intramuscular formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) for treatment of cocaine-dependent patients. Design, Setting, and Participants: A 12-week, A multicenter, randomized, placebo-controlled trial conducted between June 2009-July 2011, at 17 Hospital-based drug clinics, in the 15 countries. Participants were 18 years or older, had Diagnostic and Statistical Manual of Mental Disorders-5 cocaine use disorder. Of the 2800 patients who were assessed between March 10, 2009 to August 10, 2010, 2600 (93%) were eligible and willing to take part in the trial and were enrolled: 1300 were randomly assigned to receive injections of Long-acting depot formulations of Vanoxerine (Vanoxerine Consta 394.2 mg) given intramuscularly once in 12 weeks and 1300 to receive Placebo injections, given intramuscularly once in 12 weeks. Only 100 of 2800 patients (3.6%) did not meet the inclusion criteria. Main Outcomes and Measures: The primary endpoints (protocol) were: Confirmed Cocaine abstinence (percentage i.e. the number of patients who achieved complete abstinence during 12 weeks). Confirmed abstinence or “cocaine-free” was defined as a negative urine drug test for cocaines and no self-reported cocaine use. Secondary end points included a number of days in treatment, treatment retention and craving. The study also investigated, on 275 participants, degree and time course of Central Dopamine transporter receptor occupancy following single doses of long-acting intramuscular formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) as well as the plasma concentration of Vanoxerine and 17-hydroxyl Vanoxerine. Safety was assessed by adverse event reporting. Results: Of 2600 participants, mean (SD) age was 28.5 (±5.5) years and 598 (23%) were women. 1300 individuals were randomized to receive injections of Long-acting depot formulations of Vanoxerine (Vanoxerine Consta 394.2 mg) and 1300 to receive injections of Placebo. 1417 participants (54.5.0%) completed the trial. Primary Endpoints: Confirmed Cocaine Abstinence: Complete abstinence was sustained by 72% (n = 936) of Vanoxerine patients (patients treated with Vanoxerine Consta 394.2 mg, long-acting depot formulations) compared with 37% (n = 481) of patients treated with Placebo, during weeks 5 - 12. The difference was significant as evaluated using a Chi-square test (χ2 = 672.34, P < 0.0001). Secondary Endpoint: Craving: A statistically and clinically significant reduction in cocaine craving was observed with Vanoxerine (Vanoxerine Consta 394.2 mg, long-acting depot formulations) vs. Placeboby week 4 (P = 0.0048), which persisted every week through 12 (P < 0.0001). Patients given Vanoxerine (Vanoxerine Consta 394.2 mg, long-acting depot formulations) had a 87% decrease in craving from baseline to 12th week. Patients given a Placebo had a 2% increase in craving from baseline to 12th week. Secondary Endpoint: Treatment Retention: Long-acting intramuscular formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) helped significantly more patients complete 12 weeks treatment (n = 936, 72%) compared with Placebo (n = 481, 37%) (χ2 = 635.53, P < 0.0001). Patients on the long-acting intramuscular formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) had longer treatment retention than patients on Placebo. Concentrations of Vanoxerine and 17-Hydroxyl Vanoxerinein Plasma: Analyses were made of 275 study samples. There was no statistically significant difference for plasma Vanoxerine concentrations between days 2 and 84 (p = 0.416). The plasma concentration of Vanoxerine were 70.4 and 94.3 ng/ml and concentrations of 17-hydroxyl Vanoxerine were 10.5 and 13.2 ng/ml, respectively. Plasma levels of Vanoxerine remained above 70 ng/ml for approximately 12 weeks after administration of Vanoxerine, long-acting depot formulations (Vanoxerine Consta 394.2 mg). PET Assessments: Very high central dopamine transporter receptor occupancy by Vanoxerine was detected 1 day after treatments, at which time point the occupancy was 100.0% after Vanoxerine injection (Vanoxerine Consta 394.2 mg). At days 7, 28, 56 and 84 post-Vanoxerine Consta 394.2 mg administration, occupancies were 95% to 79%. Vanoxerine Consta 394.2 mg injection (long-acting intramuscular formulation of Vanoxerine) led to very high occupancy of Central Dopamine transporter receptors in all brain areas examined;nucleus accumbens, caudate nucleus and putamen. Depending on the brain area Central Dopamine transporter receptor occupancy varied between 95.0% and 79% at days 7, 28, 56 and 84 after dosing. High Vanoxerine occupancy (77%) persisted at 12 weeks after the dosings. Adverse Reactions: Adverse events were similar in cocaine-dependent patients treated with the long-acting intramuscular formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) vs. patients treated with Placebo. Conclusions and Relevance: Long-acting depot formulations of Vanoxerine (Vanoxerine Consta 394.2 mg) were more effective than Placebo injection in maintaining short-term abstinence from cocaine and should be considered as a treatment option for cocaine-dependent individuals.
文摘Risperidone long-acting injectable (RLAI) is approved for the treatment of schizophrenia in many countries. The suggested site is the gluteal muscle with a needle length of two inches (50 mm) in Japan, which is longer than the ordinarily used needle for intramuscular injections. The aim of this study was to determine the optimal needle insertion length for accurate delivery of RLAI procedure among subjects who have normal body mass index (BMI: 18 to 25) and high BMI (>25). Thirty-seven patients with schizophrenia were administered RLAI intramuscularly into the dorsogluteal muscle. The standard procedure required inserting 80% of the two inch needle. By using data collected by ultrasonography, the findings confirmed that the median needle insertion lengths for subjects with normal and high BMI were 39.0 and 45.5 mm, respectively. To deliver RLAI effectively and safely, the authors strongly recommend that a specialized needle be used that is “marked” at the 40 mm point from the tip of the needle to the base. In this way regardless of subcutaneous fat content, the RLAI can be safely delivered into the muscle without causing untoward or side effects.
文摘BACKGROUND Women with a history of serious psychotic disorders are at increased risk of disease relapse during pregnancy.Long-acting injectable(LAI)antipsychotics have been widely used to improve adherence and prevent relapse in patients with various severe psychotic disorders,but there is a lack of high-quality data from previous research on the safety of LAI antipsychotics during pregnancy.AIM To summarize relevant data on maternal,pregnancy,neonatal,and developmental outcomes from published cases of LAI antipsychotic use in pregnancy.METHODS A literature search was performed through November 11,2023,using three online databases:PubMed/MEDLINE,Scopus,and Web of Science.Case reports or case series that reported information about the outcomes of pregnancy in women who used LAI antipsychotics at any point in pregnancy,with available full texts,were included.Descriptive statistics,narrative summation,and tabulation of the extracted data were performed.RESULTS A total of 19 publications satisfied the inclusion criteria:3 case series,15 case reports,and 1 conference abstract.They reported the outcomes of LAI antipsychotic use in 74 women and 77 pregnancies.The use of secondgeneration LAI antipsychotics was reported in the majority(n=47;61.0%)of pregnancies.First-generation LAI antipsychotics were administered during 30 pregnancies(39.0%).Most of the women(approximately 64%)had either satisfactory control of symptoms or no information about relapse,while approximately 12%of them had developed gestational diabetes mellitus.A minority of cases reported adverse outcomes such as stillbirth,spontaneous abortion,preterm birth,low birth weight,congenital anomalies,and neurological manifestations in newborns.However,there were no reports of negative long-term developmental outcomes.CONCLUSION Currently available data seem reassuring,but further well-designed studies are required to properly evaluate the risks and benefits of LAI antipsychotic use during pregnancy.
文摘In some cases, if the insertion depth is shallower than expected, intramuscular (IM) injection of risperidone long-acting injectable (RLAI) may not penetrate the muscle fascia. However, if needle insertion depth is deeper than anticipated, needle penetration may cause damage to nerves, arteries and veins. Few clinical studies were done to evaluate the depth of needle length insertion reaching the intended gluteal muscle. The aim of this study was to evaluate the suitable depth of injecting RLAI. Twenty-six patients with schizophrenia were treated with RLAI, and randomly divided into two groups: 50 mm needle inserted group (Group-D, deep insertion, n = 13) and 20 mm needle insertion group (Group-S, shallow insertion, n = 13). For Group-S, the needle length was marked with a spacer at exactly 20 mm. Injections were performed by the psychiatrist or nurse, alternating between the two gluteal sites by double-cross method every two weeks. Clinical psychotic symptoms and injection site reactions were recorded throughout the study period. Experienced psychologists who were blinded from the needle-length experimental variable evaluated patients’ psychotic symptoms using the Positive and Negative Syndrome Scale (PANSS) every two weeks. The plasma 9-hydroxyrisperidone (9-OH-RIS) concentrations were measured every two weeks;comparison data were determined on the 8th week and the 14th week. No significant difference was observed in 9-OH-RIS concentrations, psychotic symptoms, injection site skin reactions of subjects in both groups. However, in Group-D, injection site adverse reactions were confirmed in two subjects (15%). In Group-S, injection site reactions were confirmed in six subjects (46%). Although effective 9-OH-RIS concentrations were obtained with the insertion using both depth, it was concluded that the 50 mm insertion length was more suitable for dorsogluteal IM injections in adult patients with schizophrenia as demonstrated by the incidence of local adverse skin reactions.
文摘The objectives of e-STAR Romania (NCT00283517) were to collect clinical outcome data of Romania schizophrenia or schizo-affective disorder patients;prospectively to assess the reasons of treatment initiation, medication usage patterns;to document (long-term) clinical efficacy;and to collect safety data, as well as recording 2-year corresponding retrospective data. In total, 378 eligible subjects were enrolled who were initiated either on risperidone long-acting injectable (RLAI) (290) or on an oral antipsychotic (OA) (88) at baseline as required by the local Summary of the Product Characteristics. Data were collected from per patient both retrospectively and prospectively over a 24-month period at 3-month intervals after starting treatment. The results indicated that subjects suffering from schizophrenia or schizo-affective disorder initiated on RLAI were less likely to be hospitalized within the first 24 months after the initiation of treatment. Moreover, subjects treated with RLAI experienced significant improvements in their illness severity and functioning. Discontinuation rates for RLAI were low and doses were stable throughout the 24 months following the initiation of treatment. In addition, the necessity for supplementary concomitant medication was reduced. Adverse events were reported in 20.3% (RLAI) and 11.4% (OA) of the subjects. In general, patients initiated on RLAI and OA at baseline both clinically improved on all assessed parameters but a larger improvement was observed for patients on RLAI. Incidences of reported AEs during the use of RLAI in a naturalistic setting are comparable with those described in clinical studies;however, the incidence of extrapyramidal signs and weight gain was lower than expected.
基金Foundation items:The National Major Scientific and Technological Special Project for"Significant New Drug Development"during the Twelfth Five-year Planning Period of China(Grant No.2014ZX09303303).
文摘In the present study,we aimed to determine the pharmacokinetics(PK),pharmacodynamics(PD),adverse events(AEs),and their relationships in Chinese patients with schizophrenia after a single dose of long-acting risperidone.Schizophrenic patients(six females and seven males)were enrolled in this study.Serial blood samples were collected after drug administration during 63 d,and the drug concentrations were analyzed by LC-MS/MS.Safety and tolerance were evaluated by monitoring the AEs,changes in clinical laboratory results,12-lead ECG,vital signs,physical examination,and injection-site reactions.The extrapyramidal symptoms were evaluated using the ESRS.Efficacy was evaluated by the PANSS and BPRS.Twelve out of the 13 participants completed the trial.There were few clinically meaningful changes in mean clinical laboratory values,vital signs,or ECG parameters,except for the prolactin level and body weight.There were no serious AEs,and those observed were reversible.Significant clinical improvements in PANSS and PANSS-derived BPRS total scores were observed.The mean(standard deviation,coefficient of variation)values for these PK parameters were as follows:C_(max),8.954(8.059,90.0%)ng/mL;area under the curve AUC_(0-t),2453(1156,47.1%)ng·h/mL;AUC_(0-∞),2472(1160,46.9%)ng·h/mL;t_(max),830.0(min:744.0,max:984.0,11.8%)h;and t_(1/2),68.56(10.77,15.7%)h.The PK characteristics of long-acting risperidone showed a high level of inter-individual variation,while there were no clear correlations between PK,efficacy and AEs among the patients in the present study.
基金We acknowledge financial support from the National Natural Science Foundation of China(51773098,81670817,81970772,21908019 and 21776044)Natural Science Foundation of Tianjin City of China(18JCYBJC28300)the Fundamental Research Funds for Central Universities(China).
文摘Despite advances in treatment of chronic arthritis,there is still a strong need for the development of long-acting formulations that can enable local and sustained drug release at the inflamed tissues.In this work,we fabricated microcrystals of an acid-sensitive stearoxyl-ketal-dexamethasone prodrug for treatment of arthritis.Microcrystals of the prodrug with two sizes were successfully engineered and showed pH-dependent hydrolysis kinetics in vitro.In a collagen-induced arthritis rat model,we evaluated the influence of particle size and injection dose on anti-inflammatory effect after intra-articular injection.Such prodrug demonstrated long-acting anti-arthritis effects with good safety.Our results indicate ketal-based prodrugs are promising for the development of long-acting injectables and may stimulate the development of new treatments for chronic diseases.
文摘For the quantitative determination of Fulvestrant, Benzyl alcohol, and Benzyl benzoate in Fulvestrant injection, an original RP-HPLC approach was developed. The gradient method was developed using HPLC and a Phenomenex Luna C8, 150 × 4.6 mm, i.d 3.0 μm particle size column with a gradient programme of mobile phases A and B. With a flow rate of 1.5 mL/minute, injection volume of 10 μL, and column temperature of 35°C, UV wavelength detection at 254 nm for Benzyl alcohol and Benzoyl Benzoate and 280 nm for Fulvestrant, mobile phase-A consists of DI water and mobile phase-B consists of Acetonitrile. The current study describes a single HPLC method for developing a Fulvestrant (Active), Benzyl alcohol (Cosolvent), and Benzyl Benzoate (Cosolvent) assay for Fulvestrant injection. The assay method was determined to be suitable for quantifying three components in the pharmaceutical product and was verified according to ICH guidelines.
文摘Bupivacaine encapsulated poly(lactidecoglycolide)nanoparticles is a novel formulation of extended-release of bupivacaine in poly(lactidecoglycolide)matrix.We evaluated the efficacy and safety of bupivacaine nanoparticles in peripheral analgesia via behavior tests,electrophysiological recordings,pharmacokinetic analysis,and pathology staining by employing the models of uninjured rats and mice.Nanoparticles injection increased the pain thresholds of rats and mice for 21 days.
文摘Affected by reservoir heterogeneity, there is often a serious problem of water channeling in the late stage of water injection oilfield development. Conventional water injection adjustment is difficult to further improve water drive recovery. It is necessary to adopt deep profile control and displacement technology to block water channeling channel and improve water drive efficiency.Based on the analysis of deep profile control and flooding mechanism, this paper analyzes the composition, technical indexes and adaptive conditions of seven types of profile control and flooding agent formula system, and takes block J as an example to analyze the deep adjustment effect in detail, including profile control and flooding agent system, injection volume and changes of various indexes after profile control and flooding. The effect of increasing oil and controlling water is remarkable, with an efficiency of 36.148 million yuan and an input-output ratio of 1:2.81,To achieve the purpose of cost reduction and efficiency increase under low oil prices, the achievements and understanding can provide reference experience for peers.
文摘Background Little information about the current management of patients with thyroid-stimulating hormone （TSH）-secreting pituitary adenomas or about the usefulness of the somatostatin analogue octreotide was contained in the literature. This study aimed to report the efficacy and safety of the long-acting octreotide formulation in patients with TSH-secreting pituitary adenomas after incomplete surgery and octreotide treatment failure. Methods Fifteen patients with TSH-secreting pituitary adenomas （8 men and 7 women）, who previously underwent incomplete surgical resection and/or adjuvant radiotherapy （n=12） and failure of octreotide treatment （n=15）, followed between 2007 and 2010 in Beijing Tiantan Hospital were included in this study. All patients received 1- to 2-months of the long-acting octreotide formulation treatment after the above combination of treatment. Paired samples t-test was used to analysis the variables. Results After two-month duration of the long-acting octreotide formulation treatment, the mean serum free or unbound thyroxine （FT4） （（16.02±1.72） pmol/L） and free triiodothyronine （FT3） （（2.87±0.43） pmol/L） levels of 15 patients significantly decreased compared with those after octreotide-treatment （FT4, （35.36±7.42） pmol/L, P 〈0.001; FT3, （17.85±7.22） pmol/L, P 〈0.001）. Mean TSH levels stayed in the normal range after the long-acting octreotide formulation treatment （（0.72±0.21） mUlL） and were significantly lower than the pretreatment value （（5.27±1.04） mUlL, P 〈0.001）, post-surgery value （（3.37±0.31） mU/L, P 〈0.001） and post-octreotide-treatment value （（4.52±0.41） mU/L, P 〈0.001）. In these patients with TSH-secreting pituitary adenomas there was no evidence of tachyphylaxis. Conclusion The long-acting octreotide formulation may be a useful and safe therapeutic tool to facilitate the medical treatment of TSH-secreting pituitary adenomas in patients who underwent incomplete surgery or need long-term somatostatin analog therapy.
文摘长效注射剂在治疗慢性疾病方面具有优势,本文对体外评价研究、体内评价研究的相关方法和影响因素进行了梳理,总结了体外释放行为与体内药动学过程的联立和数学建模,综述长效注射剂体内外相关性(in vitro-in vivo correlation,IVIVC)的分类、实验方法、建立步骤和模型评价方法。由于长效注射剂的多样性,IVIVC研究中不存在通用的体外模型,因此IVIVC研究只能进行逐例建模。综合药物理化性质、剂型设计和药物制剂与给药部位的相互作用对建立长效注射剂IVIVC研究十分重要。
文摘Medication adherence in patients with schizophrenia is essential for managing symptoms,improving prognosis,and enhancing the quality of life.Despite the importance of adherence,it remains a global challenge.It is influenced by various factors,including symptom severity(e.g.,excitement and impulse control disorders),attitudes towards medication(e.g.,pharmacophobia),lack of social support,and the communication efficacy of healthcare teams.Regarding assessment tools,self-report questionnaires,such as the Morisky Scale,are common but subject to recall bias.Electronic monitoring devices(e.g.,Medication Event Monitoring System)and pharmacy refill data offer more objective measures of adherence,whereas biomarkers,such as blood drug concentration monitoring,show promise under specific conditions but require further validation.Long-acting injectable antipsychotic medications have shown greater adherence benefits than oral medications.Psychological interventions such as motivational interviewing and mindfulness training,along with multidisciplinary team efforts,including psychiatrists,pharmacists,and psychotherapists,can significantly improve patient outcomes.Future research should integrate innovative drug formulations(e.g.,long-acting,low-side-effect medications),digital health technologies(e.g.,medication reminder apps and wearable devices),and supportive policies(e.g.,community-based free medication services)as well as patient education to enhance disease awareness.However,the ethical and legal dilemmas(e.g.,balancing patient autonomy with involuntary medication)and privacy concerns in technological applications require further exploration.In conclusion,enhancing medication adherence in patients with schizophrenia requires a personalized,multifaceted approach,and collaborative efforts across various sectors to achieve optimal clinical results and social functioning.
文摘利用14%吡虫啉.敌敌畏注干液剂、4.15%吡虫啉.阿维菌素注干液剂、4.5%吡虫啉注干液剂、10%啶虫脒注干液剂和30%敌畏.氧乐注干液剂等5种药剂进行了树干注射防治危害柳树的光肩星天牛(Anop lophora g labrip enn is(M otschu lsky))试验,并研究了14%吡虫啉.敌敌畏注干液剂田间防治光肩星天牛的使用技术。结果表明,供试的5种注干药剂对光肩星天牛幼虫均有一定的防治作用,其中14%吡虫啉.敌敌畏注干液剂防效最好。14%吡虫啉.敌敌畏注干液剂以1.0 mL/cm树干胸径注药量对天牛幼虫的防效可达90.7%,优于对照药剂30%敌畏.氧乐注干液剂。利用14%吡虫啉.敌敌畏注干液剂林间防治天牛时,当幼虫虫口密度低于1.15头/株时,1年注药1次;虫口密度约为5头/株时,1年注药2次;虫口密度约为12头/株时,两年注药3次,可将虫口密度控制到0.15头/株以下,有效控制天牛的危害。
