AIM:To assess the effects of the fixed combination of0.005% latanoprost and 0.5% timolol(FCLT) vs their individual components for primary open angle glaucoma(POAG) and ocular hypertension(OHT).· METHODS:After sea...AIM:To assess the effects of the fixed combination of0.005% latanoprost and 0.5% timolol(FCLT) vs their individual components for primary open angle glaucoma(POAG) and ocular hypertension(OHT).· METHODS:After searched PubMed, EMBASE, the Cochrane Library and SCI, all randomized controlled clinical trials(RCTs) and cross-over studies were included. The control groups were the monotherapy or the concomitant therapy of latanoprost and timolol. The outcomes were visual field defect, optic atrophy, mean intraocular pressure(IOP) and IOP fluctuation. The analysis was carried out in RevMan version 5.1 software.RESULTS:Thepost-interventionmeanIOPofFCLTwas significantly lower compared to timolol [mean difference(MD)-2.92, 95%CI-3.28 to-2.55, P 【0.00001] and latanoprost(MD-1.11, 95%CI-1.51 to-0.72, P 【0.00001). The postintervention IOP fluctuation was also significantly lower compared to timolol(MD-0.88, 95%CI-1.23 to-0.53, P 【0. 00001) and latanoprost( MD- 0. 63, 95 % CI- 1. 04to-0.22, P =0.002). The mean IOP was higher in FCLT morning dose group than the one in unfixed combination of 0.005% latanoprost and 0.5% timolol(UFCLT)(MD1.10, 95% CI 0.81 to 1.39, P 【0.00001). Otherwise, there was no difference between FCLT evening dose group and UFCLT(MD 0.34, 95% CI-0.01 to 0.69, P =0.06).There was no statistical difference for the incidence ofvisual field defect and optic atrophy between FCLT and the monotherapy of components.CONCLUSION:A better IOP lowering effect has been demonstrated for FCLT compared to the monotherapy of components. The IOP lowering effect was worse for FCLT morning dose and almost same for FCLT evening dose compared to the UFCLT. We need more long-term high quality RCTs to demonstrate the outcomes of visual field defect and optic atrophy.visual field defect and optic atrophy between FCLT and the monotherapy of components.CONCLUSION:A better IOP lowering effect has been demonstrated for FCLT compared to the monotherapy of components. The IOP lowering effect was worse for FCLT morning dose and almost same for FCLT evening dose compared to the UFCLT. We need more long-term high quality RCTs to demonstrate the outcomes of visual field defect and optic atrophy.展开更多
AIM:To evaluate the efficacy and tolerability of the fixed combination of bimatoprost 0.03%and timolol 0.5%(BTFC)in patients in Greece with primary open angle glaucoma(POAG)or ocular hypertension(OHT)whose previous th...AIM:To evaluate the efficacy and tolerability of the fixed combination of bimatoprost 0.03%and timolol 0.5%(BTFC)in patients in Greece with primary open angle glaucoma(POAG)or ocular hypertension(OHT)whose previous therapy provided insufficient lowering of intraocular pressure(IOP).·METHODS:A multicenter,prospective,open-label,non-interventional,observational study of the use of BTFC in clinical practice was conducted at 41 sites in Greece.The primary endpoint was the reduction in IOP from baseline at study end,approximately 12wk after initiation of BTFC therapy.·RESULTS:A total of 785 eligible patients were enrolled in the study and 97.6%completed the study.The mean±SD IOP reduction from baseline at 12wk after initiation of BTFC was 6.3±2.8 mm Hg(=764;〈0.001).In patients(=680)who replaced their previous IOP-lowering monotherapy(a single drug,or a fixed combination of 2drugs in a single ophthalmic drop)with once-daily BTFC,the mean±SD IOP reduction from baseline at 12wk was 6.2±2.8 mm Hg(〈0.001).IOP was reduced from baseline in 99.2%of patients,and 58.0%of patients reached or exceeded their target IOP.Substantial mean IOP reductions were observed regardless of the previous therapy.BTFC was well tolerated,with 96.0%of patients who completed the study rating the tolerability of BTFC as"good"or"very good."Adverse events were reported in 8.3%of patients;only 0.6%of patients discontinued the study due to adverse events.·C ONCLUSION:In clinical practice in Greece,BTFC is well tolerated and effectively lower the IOP in patients with POAG or OHT who requires additional IOP lowering on their previous therapy.展开更多
AIM: To evaluate the short-term effect of the fixed combination of brinzolamide-timolol on the ocular surface in glaucoma patients. METHODS: This is a prospective study of 23 eyes of 23 patients with newly diagnosed g...AIM: To evaluate the short-term effect of the fixed combination of brinzolamide-timolol on the ocular surface in glaucoma patients. METHODS: This is a prospective study of 23 eyes of 23 patients with newly diagnosed glaucoma. Schirmer Ⅰ test, tear break-up time (BUT) measurement, conjunctival impression cytology and central corneal thickness (CCT) measurements were performed in one of the eyes of each patients before and 4 weeks after brinzolamide-timolol fixed combination therapy. All patients were asked to answer the OSDI questionnaire form about the ocular surface symptoms at baseline and at 1 week and 4 weeks follow-up visits. RESULTS: After brinzolamide-timolol fixed combination theraphy, Schirmer Ⅰ, BUT and CCT values decreased but the only statistically significant decrease was seen in BUT test (P =0.03). OSDI scores increased during the follow-up but this increase was not statistically significant (P =0.22, P = 0.42 respectively). Impression cytology findings ranged from 0.78±0.42 to 0.95±0.36 according to the Nelson classification. There was no statistically significant difference between baseline and 4 weeks follow up in impression cytology grades (P =0.15). CONCLUSION: The results of our study indicate that short-term use of brinzolamide-timolol fixed combination theraphy does not have a profound effect on ocular surface except BUT values.展开更多
AIM： To draw a Meta-analysis over the comparison of the intraocular pressure （lOP）-lowering efficacy and safety between the commonly used fixed-combinations of prostaglandin analogs and 0.5% timolol with prostaglan...AIM： To draw a Meta-analysis over the comparison of the intraocular pressure （lOP）-lowering efficacy and safety between the commonly used fixed-combinations of prostaglandin analogs and 0.5% timolol with prostaglandin analogs （PGAs） monotherapy. METHODS： After searching the published reports from MEDLINE, EMBASE, the Cochrane Library, all randomized controlled clinical trials （RCTs） comparing the fixed combination of PGAs/timolol therapy （FCs） and PGAs monotherapy with treatment duration at least 6mo were included. The efficacy outcomes were mean diurnal lOP, percentage of participants whose lOP were lower than 18 mm Hg, incidence of visual field change, while the safety outcomes included corneal side effects, hyperemia and eye irritation. The analysis was carried out in RevMan version 5.3 software. RESULTS： After six-month medical intervention, the mean diurnal lOP of FCs was lower than PGAs （MD -1.14, 95% CI -1.82 to -0.46, P=0.001）; the percentage of target lOP achieving between FCs and PGAs showed no significant difference （RR 1.18, 95% Cl 0.97 to 1.43, P=0.10）. No statistically significant differences of the incidence of hyperemia （RR 0.67, 95% CI 0.45 to 1.01, p=0.06） and eye irritation （RR 1.20, 95% CI 0.95 to 1.51, P=0.12） between the FCs and PGAs monotherapy were detected. Only one research involved in corneal events, result of this trial revealed no difference between two intervention groups regarding corneal effects （central endothelial cell density, MD -0.20, 95% CI -0.72 to 0.32, P=0.45; central corneal thickness, MD -0.01, 95% Cl -0.02 to 0.00, P=0.23）. The evaluation of visual field change was not performed due to the limited duration of the trials included in this Meta-analysis. CONCLUSION： The long-term efficacy of the FCs overweighed the PGAs monotherapy in lowering lOP, but in the incidence of hyperemia and eye irritation syndromes, the differences are not statically significant. More RCTs with detailed and authentic data over the assessments of visual functions and morphology of optic nerve heads are hoped to be conducted.展开更多
AIM:To evaluate whether latanoprost/timolol fixed combination(LTFC)dosed twice daily may provide further intraocular pressure(IOP)reduction and evaluate the safety profile at this dose.METHODS:This is an open-labeled,...AIM:To evaluate whether latanoprost/timolol fixed combination(LTFC)dosed twice daily may provide further intraocular pressure(IOP)reduction and evaluate the safety profile at this dose.METHODS:This is an open-labeled,randomized,prospective crossover study on fourty primary open angle glaucoma patients.Two weeks of washout period were followed by randomization to either once daily(OD,group A)or twice daily dosing(BD,group B)of LTFC for 4wk.After another 2-week washout period,the patients’treatment dose was crossed-over for another 4wk.IOP reduction alongside ocular and systemic side effects were evaluated.RESULTS:Mean baseline IOP was 18.57±2.93 and 17.8±3.01 mm Hg before OD and BD dose respectively,(P=0.27).Mean IOP after BD dose was statistically lower(12.49±1.59 mm Hg)compared to OD(13.48±1.81 mm Hg,P=0.017).Although IOP reduction after BD dose was more(5.32±3.24 mm Hg,29.89%)than after OD dosing(5.04 mm Hg,27.14%),it did not reach statistical significance(P=0.68).Patients switched from OD to BD(group A)showed mean IOP reduction by 0.69 mm Hg[95%confidence interval(CI):-0.09 to 1.48 mm Hg,P=0.078];but patients switched from BD to OD(group B)had significantly higher mean IOP by 1.25 mm Hg(95%CI:-2.04 to-0.46 mm Hg,P=0.006).BD dose had more ocular side effects albeit mild.CONCLUSION:Mean IOP after LTFC dosed twice daily is statistically lower,with additional mild side effects.展开更多
AIM:To evaluate the long-term response to the fixed combination of dorzolamide/timolol in patients with primary open angle glaucoma(POAG)and the addition of other intraocular pressure(IOP)lowering medications such as ...AIM:To evaluate the long-term response to the fixed combination of dorzolamide/timolol in patients with primary open angle glaucoma(POAG)and the addition of other intraocular pressure(IOP)lowering medications such as prostaglandin analogs and brimonidine.METHODS:A retrospective,non-randomized,and descriptive clinical study was performed with 182 eyes diagnosed with POAG.Patients were divided into three groups:a group with fixed combination of dorzolamide/timolol only,a second group with prostaglandin analogs plus fixed combination of dorzolamide/timolol,and a third group with the addition of brimonidine to the same fixed combination.IOP data were gathered retrospectively and the differences between groups were calculated.RESULTS:IOP was reduced satisfactorily in all three groups;however,a progressive IOP reduction was noted in the group with the fixed combination plus prostaglandin analogs.In this group,a progressive,significant and more homogeneous response of the reduction was noted in comparison with the other groups.CONCLUSION:IOP reduction was efficacious in all three groups.The addition of prostaglandin analogs showed progressive IOP reduction,progressive responseand absence of long-term drift.Brimonidine did not show a significant additive effect.展开更多
Purpose: To compare intraocular pressure (IOP)-lowering efficacy and safety of travoprost 0.004% and travoprost 0.004% and beta-blocker 0.5% fixed combination ophthalmic solution in patients with open-angle glaucoma a...Purpose: To compare intraocular pressure (IOP)-lowering efficacy and safety of travoprost 0.004% and travoprost 0.004% and beta-blocker 0.5% fixed combination ophthalmic solution in patients with open-angle glaucoma and ocular hypertension. Methods: In this prospective, multicentre clinical trial, 62 patients received travoprost 0.004% (n = 31) or travoprost 0.004% and beta-blocker 0.5% fixed combination (n = 31). Efficacy and safety were compared across treatment groups over 2 years. IOP reduction and adverse events were examined at 3, 6, 12 and 24 months for each group. Results: Mean IOP at the first visit in the travoprost 0.004% group was 26.4 (SD ± 2.1), and travoprost 0.004%/timolol 0.5% group was 26.3 (SD ± 2.1). Mean IOP after 24 months in the travoprost 0.004% group was 20.5 (SD ± 1.5) and travoprost 0.004%/timolol 0.5% group was 18.5 (SD ± 1.5). There were statistically significant differences in IOP in both eyes after third visit (after 1 year) and fourth visit (after 2 years). Conclusion: After 2 year of treatment, travoprost 0.004%/timolol 0.5% produced clinically relevant IOP reductions in patients with open-angle glaucoma or ocular hypertension that were greater than those produced by travoprost 0.004% alone.展开更多
Arterial hypertension is the leading risk mortality factor in the world according to the report by the World Health Organization. The aim of this research was to compare fixed-dose combination with free-drug combinati...Arterial hypertension is the leading risk mortality factor in the world according to the report by the World Health Organization. The aim of this research was to compare fixed-dose combination with free-drug combination therapy and prove that fixed-dose combination improve patient compliance and persistence, measuring blood pressure among hypertensive patients in a Croatian Adriatic city. Methods： The study included 202 patients, 101 women and 101 men, mean age 66.8 4- 9.4 with previous diagnosis of hypertension. Results： Mean blood pressure was 152.8 4- 18.8/87.3 4- 10.3 mmHg. Blood pressure control 140/90 mmHg） was achieved in 24.8% of patients, 13.9% of women and 10.9% of men. Mean blood pressure in the group with fixed-dose combination was 149.2 4- 17.9/86.2 4- 8.5 mmHg, and 156.7 4- 18.9/88.4 4- 11.8 mmHg in the group with free-drug combination therapy. Conclusions： Results suggest that blood pressure control was better in patients with fixed-dose combinations than in patients with free-drug combinations. Fixed-drug combination improved compliance and adherence in patients with antihypertensive therapy. Results of the study indicate that fixed-drug combination should be considered in patients with hypertension according to the guidelines.展开更多
Background: This study evaluated the bioequivalence of empagliflozin 12.5 mg/metformin 1000 mg tablets compared to Synjardy® (Empagliflozin 12.5 mg/metformin 1000 mg) tablets in healthy male subjects under fastin...Background: This study evaluated the bioequivalence of empagliflozin 12.5 mg/metformin 1000 mg tablets compared to Synjardy® (Empagliflozin 12.5 mg/metformin 1000 mg) tablets in healthy male subjects under fasting conditions. Methods: This was a phase I, randomized, single-dose, two-period, two-sequence, crossover study to evaluate the bioequivalence (BE) profiles of two fixed-dose combinations (FDCs) of empagliflozin/metformin. Cmax, AUC0-t and AUC0-∞ from test and reference formulations were evaluated to access BE. The plasma concentrations were measured using a validated liquid chromatography-mass spectrometry (LC-MS/MS) method. Of the 24 subjects enrolled, 23 completed both periods of the study. The two formulations test and reference were considered bioequivalent if 90% confidence interval (CI) fell within 80.00% - 125.00% for Cmax, AUC0-t and AUC0-∞. Tolerability and safety were assessed throughout the study. Results: The pharmacokinetic (PK) parameters were similar between the test product (T) and reference product (R) Synjardy®. The 90% CI of the test/reference ratios of log-transformed PK parameters point estimates was Cmax: 89.87% (85.68% - 94.27%), AUC0-t: 87.91% (83.65% - 92.39%) and AUC0-∞: 87.16% (82.80% - 91.75%) to empagliflozin and Cmax: 92.19% (87.95% - 96.65%), AUC0-t: 91.38% (84.42% - 98.91%) and AUC0-∞: 93.78% (83.82% - 104.93%) to metformin respectively (90% CI for all PK parameters fell within 80.00% - 125.00%). Conclusion: Our results demonstrated BE between the test and reference formulations of oral tablets of empagliflozin 12.5 mg/metformin 1000 mg (FDC) in healthy male subjects under fasting conditions.展开更多
Background Lowering intraocular pressure （lOP） is currently the only therapeutic approach in primary open-angle glaucoma.and the fixed-combination medications are needed to achieve sufficiently low target lOP.A mult...Background Lowering intraocular pressure （lOP） is currently the only therapeutic approach in primary open-angle glaucoma.and the fixed-combination medications are needed to achieve sufficiently low target lOP.A multicenter prospective study in the Chinese population was needed to confirm the safety and efficacy of Bimatoprost/Timolol Fixed Combination Eye Drop in China.In this study,we evaluated the safety and efficacy of Bimatoprost/Timolol Fixed Combination with concurrent administration of its components in Chinese patients with open-angle glaucoma or ocular hypertension.Methods In this multicenter,randomized,double-masked,parallel controlled study,patients with open-angle glaucoma or ocular hypertension who were insufficiently responsive to monotherapy with either topical β-blockers or prostaglandin analogues were randomized to one of two active treatment groups in a 1：1 ratio at 11 Chinese ophthalmic departments.Bimatoprost/timolol fixed combination treatment was a fixed combination of 0.03％ bimatoprost and 0.5％ timolol （followed by vehicle for masking） once daily at 19：00 P.M.and concurrent treatment was 0.03％ bimatoprost followed by 0.5％ timolol once daily at 19：00 P.M.The primary efficacy variable was change from baseline in mean diurnal intraocular pressure （IOP） at week 4 visit in the intent-to-treat （ITr） population.Primary analysis evaluated the non-inferiority of bimatoprost/timolol fixed combination to concurrent with respect to the primary variable using a confidence interval （CI） approach.Bimatoprost/timolol fixed combination was to be considered non-inferior to concurrent if the upper limit of the 95％ CI for the between-treatment （bimatoprost/timolol fixed combination minus concurrent） difference was-≤1.5 mmHg.Adverse events were collected and slit-lamp examinations were performed to assess safety.Between-group comparisons of the incidence of adverse events were performed using the Pearson chi-square test or Fisher＇s exact test.Results Of the enrolled 235 patients,121 patients were randomized to receive bimatoprost/timolol fixed combination and,114 patients were randomized to receive concurrent treatment.At baseline the mean value of mean diurnal IOP was （25.20±3.06） mmHg in the bimatoprost/timolol fixed combination group and （24.87±3.88） mmHg in the concurrent group.The difference between the treatment groups was not statistically significant.The mean change from baseline in mean diurnal IOP （±standard deviation） in the bimatoprost/timolol fixed combination group was （-9.38±4.66） mmHg and it was （-8.93±4.25） mmHg in the concurrent group （P ＜0.01）.The difference between the two treatment groups （bimatoprost/timolol fixed combination minus concurrent） in the change from baseline of mean diurnal IOP was-0.556 mmHg （95％ CI：-1.68,0.57,P=0.330）.The upper limit of the 95％ CI was less than 1.5 mmHg,the predefined margin of non-inferiority.Adverse events occurred in 26.4％ （32/121）of the bimatoprost/timolol fixed combination patients and 30.7％ （35/114） of the concurrent patients.The most frequent adverse event was conjunctival hyperemia,which was reported as treatment related in 16.5％ （20/121） in the bimatoprost/timolol fixed combination group and 18.4％（21/114） in the concurrent group （P ＞0.05）.Conclusions Bimatoprost/Timolol Fixed Combination administered in Chinese patients with open-angle glaucoma or ocular hypertension was not inferior to concurrent dosing with the individual components.Safety profiles were similar between the treatment groups.展开更多
BACKGROUND Fixed ratio combinations(FRCs)of analogue basal insulin and glucagon-like peptide-1 receptor agonists are a newer addition to the therapeutic armamentarium for the management of type 2 diabetes mellitus.The...BACKGROUND Fixed ratio combinations(FRCs)of analogue basal insulin and glucagon-like peptide-1 receptor agonists are a newer addition to the therapeutic armamentarium for the management of type 2 diabetes mellitus.They reduce treatment complexity by combining two injectables in a single daily injectable,thus potentially improving adherence and persistence.Clinicians wanting to use FRCs would need to choose between members of the class.AIM To describe and contrast the glycated haemoglobin reduction of two FRCs of analogue basal insulin and glucagon like peptide-1 receptor agonist in adults with type 2 diabetes mellitus.METHODS The following Population,Intervention,Comparison,Outcome question was used for the primary analysis:Among adult patients with type 2 diabetes mellitus[P],what is the effect of iGlarLixi[I]compared to IDegLira[C]for bringing about glycaemic control(as measured by reduction in glycosylated haemoglobin)[O]?The Prisma Statement was used as a guideline for framing this systematic review.We searched PubMed,EMBASE and Cochrane library databases and Clinicaltrials.gov using various keywords and medical search headings related to type 2 diabetes mellitus,iGlarlixi,IDegLira and glycated haemoglobin A1c.RESULTS All 14 studies identified by the systematic search met the primary efficacy endpoint of reduction in glycated haemoglobin.There were no head-to-head studies between the FRCs of iGlarlixi and IDegLira,and we therefore did an indirect comparison based on a common comparator of insulin glargine U100.Both iGlarLixi and IDegLira effectively reduce glycated haemoglobin when compared to insulin glargine U100.However,using indirect comparisons,IDegLira had a greater haemoglobin A1c reducing ability(0.6%vs 0.3%).The indirect comparison is limited by the differences between the studies;the fasting blood glucose targets were slightly higher for iGlarLixi studies when compared to the IDegLira studies(4.0-5.0 mmol/L and 4.4-5.6 mmol/L),and the IDegLira study used a greater average dose of insulin glargine when compared to the iGlarLixi studies(66 U/d vs 40 U/d).CONCLUSION Both iGlarLixi and IDegLira effectively reduce glycated haemoglobin.Indirect comparisons,using insulin glargine as the common comparator,suggest that IDegLira reduces glycated haemoglobin to a greater extent than iGlarLixi.However,given the limitations of indirect comparisons,robust head to head studies and real-world data would better inform clinician choice and clinical practice guidelines.展开更多
Background： Combination of angiotensin-converting enzyme inhibitors and calcium channel blockers has been successfully used in the ant±hypertensive therapy for many years. Fixed dose combinations of ramipril/aml...Background： Combination of angiotensin-converting enzyme inhibitors and calcium channel blockers has been successfully used in the ant±hypertensive therapy for many years. Fixed dose combinations of ramipril/amlodipine have a benefit effect for patients to achieve target blood pressure （BP）. This study aimed to assess the efficacy and safety of fixed dose combinations oframipril and amlodipine （Egiramlon） in hypertensive diabetic patients. Methods： Hypertensive diabetic patients who were enrolled into the RAMONA trial were included in this open, prospective, Phase Ⅳ observational clinical study. Patients had mild-to-moderate hypertension and failed to reach target BP levels through their previous therapy. During the four months of observation, patients took part in three visits （1 st day - visit 1, 1 st month = visit 2, and 4th month = visit 3） where they received a fixed dose combination of 5/5, 5/10, 10/5, or 10/10 nag ramipril/amlodipine, respectively, with the possibly required dose titrations, based on the decision of their attending physician. Target BP for diabetic patients was 〈 140/85 mmHg. BP levels were measured in all visits, by taking two readings at 2-min interval. Laboratory tests including full blood count, renal function test, electrolytes, blood glucose, serum cholesterol, uric acid, triglycerides, liver function test, creatinine kinase, and midstream urinalysis were performed at visit 1 and visit 3. Results： The 6423 patients completed the study. Among these patients, 1276 （19.9%） patients suffered from type 2 diabetes mellitus. The mean age of these diabetic patients was 64.2 ±10.0 years; 707 （55.4%） patients were males. Target BP was achieved by 891 （69.8%） of diabetic patients at visit 3 （primary endpoint）. BP decreased from 157.5/91.3 ±9.6/7.6 mmHg （visit 1） to 130.9/79.6 ± 7.4/5.8 mmHg （visit 3）. As for the secondary endpoint of the study, total cholesterol decreased from 5.50 ±1.13 mmol/L （visit 1 ） to 5.20 ±0.95 mmol/L （P = 0.000）, low-density lipoprotein cholesterol decreased from 3.20 ±0.93 mmol/L to 3.00 ±0.77 mmol/L （P = 0.000）, triglyceride decreased from 2.20 ±1.14 mmol/L to 2.00 ±1.97 mmol/L （P = 0.000）, while high-density lipoprotein cholesterol increased from 1.30 ±0.42 to 1.35 ±0.30 mmol/L （P = 0.001） until the end of the 4th month （visit 3）. Fasting blood glucose of the hypertensive diabetic patients decreased from 7.20 ± 1,88 mmol/L to 6.70 ± 1.38 mmol/L （P = 0.000）, while HbAlc decreased from 7.90 ± 1.78% to 7.60 ± 1.83% （P = 0.000）. Various fixed dose combinations of ramipril/amlodipine were well tolerated and no adverse event related to the use of the medicine has appeared. Conclusions： The fixed dose combination of ramipril/amlodipine was effective in hypertensive diabetic patients who failed to reach target BP previously.展开更多
We developed a novel portable and automated dissolution test analyzer for rapid and high precision in vitro dissolution testing of drugs.The analyzer consists of a flow-through-cell drug dissolution system,an automate...We developed a novel portable and automated dissolution test analyzer for rapid and high precision in vitro dissolution testing of drugs.The analyzer consists of a flow-through-cell drug dissolution system,an automated sequential sampling system,a high-speed capillary electrophoresis(HSCE)system,and a data acquisition system.Combining the high-temporal resolution flow-gating sampling approach with HSCE,which has outstanding advantages of efficient separation and resolution,the analyzer can achieve rapid analysis and exhibits the ability in miniaturization for on-site assessment of different active pharmaceutical ingredients.To integrate the flow-through-cell dissolution system with HSCE,a specially designed flow-gating-injection(FGI)interface was employed.The performance of the analyzer was investigated by analyzing the dissolution of immediate-release drugs including single dose(amoxicillin dispersible tablets)and fixed dose combination(amoxicillin and clavulanate potassium)drug tablets with the high-temporal resolutions of 12 s and 20 s,respectively.The dissolution profiles of different active pharmaceutical ingredients could be simultaneously and automatically monitored with high repeatability and accuracy.The analyzer was successfully utilized for the pharmaceutical quality control and bio-relevant dissolution testing,as well as in vivo-in vitro correlation analysis.Our portable analyzer is miniaturized,convenient and of low-cost,and will provide a valuable tool for dissolution testing in pharmaceutical research and development.展开更多
文摘AIM:To assess the effects of the fixed combination of0.005% latanoprost and 0.5% timolol(FCLT) vs their individual components for primary open angle glaucoma(POAG) and ocular hypertension(OHT).· METHODS:After searched PubMed, EMBASE, the Cochrane Library and SCI, all randomized controlled clinical trials(RCTs) and cross-over studies were included. The control groups were the monotherapy or the concomitant therapy of latanoprost and timolol. The outcomes were visual field defect, optic atrophy, mean intraocular pressure(IOP) and IOP fluctuation. The analysis was carried out in RevMan version 5.1 software.RESULTS:Thepost-interventionmeanIOPofFCLTwas significantly lower compared to timolol [mean difference(MD)-2.92, 95%CI-3.28 to-2.55, P 【0.00001] and latanoprost(MD-1.11, 95%CI-1.51 to-0.72, P 【0.00001). The postintervention IOP fluctuation was also significantly lower compared to timolol(MD-0.88, 95%CI-1.23 to-0.53, P 【0. 00001) and latanoprost( MD- 0. 63, 95 % CI- 1. 04to-0.22, P =0.002). The mean IOP was higher in FCLT morning dose group than the one in unfixed combination of 0.005% latanoprost and 0.5% timolol(UFCLT)(MD1.10, 95% CI 0.81 to 1.39, P 【0.00001). Otherwise, there was no difference between FCLT evening dose group and UFCLT(MD 0.34, 95% CI-0.01 to 0.69, P =0.06).There was no statistical difference for the incidence ofvisual field defect and optic atrophy between FCLT and the monotherapy of components.CONCLUSION:A better IOP lowering effect has been demonstrated for FCLT compared to the monotherapy of components. The IOP lowering effect was worse for FCLT morning dose and almost same for FCLT evening dose compared to the UFCLT. We need more long-term high quality RCTs to demonstrate the outcomes of visual field defect and optic atrophy.visual field defect and optic atrophy between FCLT and the monotherapy of components.CONCLUSION:A better IOP lowering effect has been demonstrated for FCLT compared to the monotherapy of components. The IOP lowering effect was worse for FCLT morning dose and almost same for FCLT evening dose compared to the UFCLT. We need more long-term high quality RCTs to demonstrate the outcomes of visual field defect and optic atrophy.
文摘AIM:To evaluate the efficacy and tolerability of the fixed combination of bimatoprost 0.03%and timolol 0.5%(BTFC)in patients in Greece with primary open angle glaucoma(POAG)or ocular hypertension(OHT)whose previous therapy provided insufficient lowering of intraocular pressure(IOP).·METHODS:A multicenter,prospective,open-label,non-interventional,observational study of the use of BTFC in clinical practice was conducted at 41 sites in Greece.The primary endpoint was the reduction in IOP from baseline at study end,approximately 12wk after initiation of BTFC therapy.·RESULTS:A total of 785 eligible patients were enrolled in the study and 97.6%completed the study.The mean±SD IOP reduction from baseline at 12wk after initiation of BTFC was 6.3±2.8 mm Hg(=764;〈0.001).In patients(=680)who replaced their previous IOP-lowering monotherapy(a single drug,or a fixed combination of 2drugs in a single ophthalmic drop)with once-daily BTFC,the mean±SD IOP reduction from baseline at 12wk was 6.2±2.8 mm Hg(〈0.001).IOP was reduced from baseline in 99.2%of patients,and 58.0%of patients reached or exceeded their target IOP.Substantial mean IOP reductions were observed regardless of the previous therapy.BTFC was well tolerated,with 96.0%of patients who completed the study rating the tolerability of BTFC as"good"or"very good."Adverse events were reported in 8.3%of patients;only 0.6%of patients discontinued the study due to adverse events.·C ONCLUSION:In clinical practice in Greece,BTFC is well tolerated and effectively lower the IOP in patients with POAG or OHT who requires additional IOP lowering on their previous therapy.
文摘AIM: To evaluate the short-term effect of the fixed combination of brinzolamide-timolol on the ocular surface in glaucoma patients. METHODS: This is a prospective study of 23 eyes of 23 patients with newly diagnosed glaucoma. Schirmer Ⅰ test, tear break-up time (BUT) measurement, conjunctival impression cytology and central corneal thickness (CCT) measurements were performed in one of the eyes of each patients before and 4 weeks after brinzolamide-timolol fixed combination therapy. All patients were asked to answer the OSDI questionnaire form about the ocular surface symptoms at baseline and at 1 week and 4 weeks follow-up visits. RESULTS: After brinzolamide-timolol fixed combination theraphy, Schirmer Ⅰ, BUT and CCT values decreased but the only statistically significant decrease was seen in BUT test (P =0.03). OSDI scores increased during the follow-up but this increase was not statistically significant (P =0.22, P = 0.42 respectively). Impression cytology findings ranged from 0.78±0.42 to 0.95±0.36 according to the Nelson classification. There was no statistically significant difference between baseline and 4 weeks follow up in impression cytology grades (P =0.15). CONCLUSION: The results of our study indicate that short-term use of brinzolamide-timolol fixed combination theraphy does not have a profound effect on ocular surface except BUT values.
基金Supported by the National Outstanding Youth Science Fund Project(No.81202726)
文摘AIM： To draw a Meta-analysis over the comparison of the intraocular pressure （lOP）-lowering efficacy and safety between the commonly used fixed-combinations of prostaglandin analogs and 0.5% timolol with prostaglandin analogs （PGAs） monotherapy. METHODS： After searching the published reports from MEDLINE, EMBASE, the Cochrane Library, all randomized controlled clinical trials （RCTs） comparing the fixed combination of PGAs/timolol therapy （FCs） and PGAs monotherapy with treatment duration at least 6mo were included. The efficacy outcomes were mean diurnal lOP, percentage of participants whose lOP were lower than 18 mm Hg, incidence of visual field change, while the safety outcomes included corneal side effects, hyperemia and eye irritation. The analysis was carried out in RevMan version 5.3 software. RESULTS： After six-month medical intervention, the mean diurnal lOP of FCs was lower than PGAs （MD -1.14, 95% CI -1.82 to -0.46, P=0.001）; the percentage of target lOP achieving between FCs and PGAs showed no significant difference （RR 1.18, 95% Cl 0.97 to 1.43, P=0.10）. No statistically significant differences of the incidence of hyperemia （RR 0.67, 95% CI 0.45 to 1.01, p=0.06） and eye irritation （RR 1.20, 95% CI 0.95 to 1.51, P=0.12） between the FCs and PGAs monotherapy were detected. Only one research involved in corneal events, result of this trial revealed no difference between two intervention groups regarding corneal effects （central endothelial cell density, MD -0.20, 95% CI -0.72 to 0.32, P=0.45; central corneal thickness, MD -0.01, 95% Cl -0.02 to 0.00, P=0.23）. The evaluation of visual field change was not performed due to the limited duration of the trials included in this Meta-analysis. CONCLUSION： The long-term efficacy of the FCs overweighed the PGAs monotherapy in lowering lOP, but in the incidence of hyperemia and eye irritation syndromes, the differences are not statically significant. More RCTs with detailed and authentic data over the assessments of visual functions and morphology of optic nerve heads are hoped to be conducted.
基金Anis Baidura Azal holds a Masters scholarship funded by the Government of MalaysiaNorshamsiah Md Din receives funding from the UKMMC Fundamental Research Fund(No.FF-2019-058)。
文摘AIM:To evaluate whether latanoprost/timolol fixed combination(LTFC)dosed twice daily may provide further intraocular pressure(IOP)reduction and evaluate the safety profile at this dose.METHODS:This is an open-labeled,randomized,prospective crossover study on fourty primary open angle glaucoma patients.Two weeks of washout period were followed by randomization to either once daily(OD,group A)or twice daily dosing(BD,group B)of LTFC for 4wk.After another 2-week washout period,the patients’treatment dose was crossed-over for another 4wk.IOP reduction alongside ocular and systemic side effects were evaluated.RESULTS:Mean baseline IOP was 18.57±2.93 and 17.8±3.01 mm Hg before OD and BD dose respectively,(P=0.27).Mean IOP after BD dose was statistically lower(12.49±1.59 mm Hg)compared to OD(13.48±1.81 mm Hg,P=0.017).Although IOP reduction after BD dose was more(5.32±3.24 mm Hg,29.89%)than after OD dosing(5.04 mm Hg,27.14%),it did not reach statistical significance(P=0.68).Patients switched from OD to BD(group A)showed mean IOP reduction by 0.69 mm Hg[95%confidence interval(CI):-0.09 to 1.48 mm Hg,P=0.078];but patients switched from BD to OD(group B)had significantly higher mean IOP by 1.25 mm Hg(95%CI:-2.04 to-0.46 mm Hg,P=0.006).BD dose had more ocular side effects albeit mild.CONCLUSION:Mean IOP after LTFC dosed twice daily is statistically lower,with additional mild side effects.
文摘AIM:To evaluate the long-term response to the fixed combination of dorzolamide/timolol in patients with primary open angle glaucoma(POAG)and the addition of other intraocular pressure(IOP)lowering medications such as prostaglandin analogs and brimonidine.METHODS:A retrospective,non-randomized,and descriptive clinical study was performed with 182 eyes diagnosed with POAG.Patients were divided into three groups:a group with fixed combination of dorzolamide/timolol only,a second group with prostaglandin analogs plus fixed combination of dorzolamide/timolol,and a third group with the addition of brimonidine to the same fixed combination.IOP data were gathered retrospectively and the differences between groups were calculated.RESULTS:IOP was reduced satisfactorily in all three groups;however,a progressive IOP reduction was noted in the group with the fixed combination plus prostaglandin analogs.In this group,a progressive,significant and more homogeneous response of the reduction was noted in comparison with the other groups.CONCLUSION:IOP reduction was efficacious in all three groups.The addition of prostaglandin analogs showed progressive IOP reduction,progressive responseand absence of long-term drift.Brimonidine did not show a significant additive effect.
文摘Purpose: To compare intraocular pressure (IOP)-lowering efficacy and safety of travoprost 0.004% and travoprost 0.004% and beta-blocker 0.5% fixed combination ophthalmic solution in patients with open-angle glaucoma and ocular hypertension. Methods: In this prospective, multicentre clinical trial, 62 patients received travoprost 0.004% (n = 31) or travoprost 0.004% and beta-blocker 0.5% fixed combination (n = 31). Efficacy and safety were compared across treatment groups over 2 years. IOP reduction and adverse events were examined at 3, 6, 12 and 24 months for each group. Results: Mean IOP at the first visit in the travoprost 0.004% group was 26.4 (SD ± 2.1), and travoprost 0.004%/timolol 0.5% group was 26.3 (SD ± 2.1). Mean IOP after 24 months in the travoprost 0.004% group was 20.5 (SD ± 1.5) and travoprost 0.004%/timolol 0.5% group was 18.5 (SD ± 1.5). There were statistically significant differences in IOP in both eyes after third visit (after 1 year) and fourth visit (after 2 years). Conclusion: After 2 year of treatment, travoprost 0.004%/timolol 0.5% produced clinically relevant IOP reductions in patients with open-angle glaucoma or ocular hypertension that were greater than those produced by travoprost 0.004% alone.
文摘Arterial hypertension is the leading risk mortality factor in the world according to the report by the World Health Organization. The aim of this research was to compare fixed-dose combination with free-drug combination therapy and prove that fixed-dose combination improve patient compliance and persistence, measuring blood pressure among hypertensive patients in a Croatian Adriatic city. Methods： The study included 202 patients, 101 women and 101 men, mean age 66.8 4- 9.4 with previous diagnosis of hypertension. Results： Mean blood pressure was 152.8 4- 18.8/87.3 4- 10.3 mmHg. Blood pressure control 140/90 mmHg） was achieved in 24.8% of patients, 13.9% of women and 10.9% of men. Mean blood pressure in the group with fixed-dose combination was 149.2 4- 17.9/86.2 4- 8.5 mmHg, and 156.7 4- 18.9/88.4 4- 11.8 mmHg in the group with free-drug combination therapy. Conclusions： Results suggest that blood pressure control was better in patients with fixed-dose combinations than in patients with free-drug combinations. Fixed-drug combination improved compliance and adherence in patients with antihypertensive therapy. Results of the study indicate that fixed-drug combination should be considered in patients with hypertension according to the guidelines.
文摘Background: This study evaluated the bioequivalence of empagliflozin 12.5 mg/metformin 1000 mg tablets compared to Synjardy® (Empagliflozin 12.5 mg/metformin 1000 mg) tablets in healthy male subjects under fasting conditions. Methods: This was a phase I, randomized, single-dose, two-period, two-sequence, crossover study to evaluate the bioequivalence (BE) profiles of two fixed-dose combinations (FDCs) of empagliflozin/metformin. Cmax, AUC0-t and AUC0-∞ from test and reference formulations were evaluated to access BE. The plasma concentrations were measured using a validated liquid chromatography-mass spectrometry (LC-MS/MS) method. Of the 24 subjects enrolled, 23 completed both periods of the study. The two formulations test and reference were considered bioequivalent if 90% confidence interval (CI) fell within 80.00% - 125.00% for Cmax, AUC0-t and AUC0-∞. Tolerability and safety were assessed throughout the study. Results: The pharmacokinetic (PK) parameters were similar between the test product (T) and reference product (R) Synjardy®. The 90% CI of the test/reference ratios of log-transformed PK parameters point estimates was Cmax: 89.87% (85.68% - 94.27%), AUC0-t: 87.91% (83.65% - 92.39%) and AUC0-∞: 87.16% (82.80% - 91.75%) to empagliflozin and Cmax: 92.19% (87.95% - 96.65%), AUC0-t: 91.38% (84.42% - 98.91%) and AUC0-∞: 93.78% (83.82% - 104.93%) to metformin respectively (90% CI for all PK parameters fell within 80.00% - 125.00%). Conclusion: Our results demonstrated BE between the test and reference formulations of oral tablets of empagliflozin 12.5 mg/metformin 1000 mg (FDC) in healthy male subjects under fasting conditions.
文摘Background Lowering intraocular pressure （lOP） is currently the only therapeutic approach in primary open-angle glaucoma.and the fixed-combination medications are needed to achieve sufficiently low target lOP.A multicenter prospective study in the Chinese population was needed to confirm the safety and efficacy of Bimatoprost/Timolol Fixed Combination Eye Drop in China.In this study,we evaluated the safety and efficacy of Bimatoprost/Timolol Fixed Combination with concurrent administration of its components in Chinese patients with open-angle glaucoma or ocular hypertension.Methods In this multicenter,randomized,double-masked,parallel controlled study,patients with open-angle glaucoma or ocular hypertension who were insufficiently responsive to monotherapy with either topical β-blockers or prostaglandin analogues were randomized to one of two active treatment groups in a 1：1 ratio at 11 Chinese ophthalmic departments.Bimatoprost/timolol fixed combination treatment was a fixed combination of 0.03％ bimatoprost and 0.5％ timolol （followed by vehicle for masking） once daily at 19：00 P.M.and concurrent treatment was 0.03％ bimatoprost followed by 0.5％ timolol once daily at 19：00 P.M.The primary efficacy variable was change from baseline in mean diurnal intraocular pressure （IOP） at week 4 visit in the intent-to-treat （ITr） population.Primary analysis evaluated the non-inferiority of bimatoprost/timolol fixed combination to concurrent with respect to the primary variable using a confidence interval （CI） approach.Bimatoprost/timolol fixed combination was to be considered non-inferior to concurrent if the upper limit of the 95％ CI for the between-treatment （bimatoprost/timolol fixed combination minus concurrent） difference was-≤1.5 mmHg.Adverse events were collected and slit-lamp examinations were performed to assess safety.Between-group comparisons of the incidence of adverse events were performed using the Pearson chi-square test or Fisher＇s exact test.Results Of the enrolled 235 patients,121 patients were randomized to receive bimatoprost/timolol fixed combination and,114 patients were randomized to receive concurrent treatment.At baseline the mean value of mean diurnal IOP was （25.20±3.06） mmHg in the bimatoprost/timolol fixed combination group and （24.87±3.88） mmHg in the concurrent group.The difference between the treatment groups was not statistically significant.The mean change from baseline in mean diurnal IOP （±standard deviation） in the bimatoprost/timolol fixed combination group was （-9.38±4.66） mmHg and it was （-8.93±4.25） mmHg in the concurrent group （P ＜0.01）.The difference between the two treatment groups （bimatoprost/timolol fixed combination minus concurrent） in the change from baseline of mean diurnal IOP was-0.556 mmHg （95％ CI：-1.68,0.57,P=0.330）.The upper limit of the 95％ CI was less than 1.5 mmHg,the predefined margin of non-inferiority.Adverse events occurred in 26.4％ （32/121）of the bimatoprost/timolol fixed combination patients and 30.7％ （35/114） of the concurrent patients.The most frequent adverse event was conjunctival hyperemia,which was reported as treatment related in 16.5％ （20/121） in the bimatoprost/timolol fixed combination group and 18.4％（21/114） in the concurrent group （P ＞0.05）.Conclusions Bimatoprost/Timolol Fixed Combination administered in Chinese patients with open-angle glaucoma or ocular hypertension was not inferior to concurrent dosing with the individual components.Safety profiles were similar between the treatment groups.
文摘BACKGROUND Fixed ratio combinations(FRCs)of analogue basal insulin and glucagon-like peptide-1 receptor agonists are a newer addition to the therapeutic armamentarium for the management of type 2 diabetes mellitus.They reduce treatment complexity by combining two injectables in a single daily injectable,thus potentially improving adherence and persistence.Clinicians wanting to use FRCs would need to choose between members of the class.AIM To describe and contrast the glycated haemoglobin reduction of two FRCs of analogue basal insulin and glucagon like peptide-1 receptor agonist in adults with type 2 diabetes mellitus.METHODS The following Population,Intervention,Comparison,Outcome question was used for the primary analysis:Among adult patients with type 2 diabetes mellitus[P],what is the effect of iGlarLixi[I]compared to IDegLira[C]for bringing about glycaemic control(as measured by reduction in glycosylated haemoglobin)[O]?The Prisma Statement was used as a guideline for framing this systematic review.We searched PubMed,EMBASE and Cochrane library databases and Clinicaltrials.gov using various keywords and medical search headings related to type 2 diabetes mellitus,iGlarlixi,IDegLira and glycated haemoglobin A1c.RESULTS All 14 studies identified by the systematic search met the primary efficacy endpoint of reduction in glycated haemoglobin.There were no head-to-head studies between the FRCs of iGlarlixi and IDegLira,and we therefore did an indirect comparison based on a common comparator of insulin glargine U100.Both iGlarLixi and IDegLira effectively reduce glycated haemoglobin when compared to insulin glargine U100.However,using indirect comparisons,IDegLira had a greater haemoglobin A1c reducing ability(0.6%vs 0.3%).The indirect comparison is limited by the differences between the studies;the fasting blood glucose targets were slightly higher for iGlarLixi studies when compared to the IDegLira studies(4.0-5.0 mmol/L and 4.4-5.6 mmol/L),and the IDegLira study used a greater average dose of insulin glargine when compared to the iGlarLixi studies(66 U/d vs 40 U/d).CONCLUSION Both iGlarLixi and IDegLira effectively reduce glycated haemoglobin.Indirect comparisons,using insulin glargine as the common comparator,suggest that IDegLira reduces glycated haemoglobin to a greater extent than iGlarLixi.However,given the limitations of indirect comparisons,robust head to head studies and real-world data would better inform clinician choice and clinical practice guidelines.
文摘Background： Combination of angiotensin-converting enzyme inhibitors and calcium channel blockers has been successfully used in the ant±hypertensive therapy for many years. Fixed dose combinations of ramipril/amlodipine have a benefit effect for patients to achieve target blood pressure （BP）. This study aimed to assess the efficacy and safety of fixed dose combinations oframipril and amlodipine （Egiramlon） in hypertensive diabetic patients. Methods： Hypertensive diabetic patients who were enrolled into the RAMONA trial were included in this open, prospective, Phase Ⅳ observational clinical study. Patients had mild-to-moderate hypertension and failed to reach target BP levels through their previous therapy. During the four months of observation, patients took part in three visits （1 st day - visit 1, 1 st month = visit 2, and 4th month = visit 3） where they received a fixed dose combination of 5/5, 5/10, 10/5, or 10/10 nag ramipril/amlodipine, respectively, with the possibly required dose titrations, based on the decision of their attending physician. Target BP for diabetic patients was 〈 140/85 mmHg. BP levels were measured in all visits, by taking two readings at 2-min interval. Laboratory tests including full blood count, renal function test, electrolytes, blood glucose, serum cholesterol, uric acid, triglycerides, liver function test, creatinine kinase, and midstream urinalysis were performed at visit 1 and visit 3. Results： The 6423 patients completed the study. Among these patients, 1276 （19.9%） patients suffered from type 2 diabetes mellitus. The mean age of these diabetic patients was 64.2 ±10.0 years; 707 （55.4%） patients were males. Target BP was achieved by 891 （69.8%） of diabetic patients at visit 3 （primary endpoint）. BP decreased from 157.5/91.3 ±9.6/7.6 mmHg （visit 1） to 130.9/79.6 ± 7.4/5.8 mmHg （visit 3）. As for the secondary endpoint of the study, total cholesterol decreased from 5.50 ±1.13 mmol/L （visit 1 ） to 5.20 ±0.95 mmol/L （P = 0.000）, low-density lipoprotein cholesterol decreased from 3.20 ±0.93 mmol/L to 3.00 ±0.77 mmol/L （P = 0.000）, triglyceride decreased from 2.20 ±1.14 mmol/L to 2.00 ±1.97 mmol/L （P = 0.000）, while high-density lipoprotein cholesterol increased from 1.30 ±0.42 to 1.35 ±0.30 mmol/L （P = 0.001） until the end of the 4th month （visit 3）. Fasting blood glucose of the hypertensive diabetic patients decreased from 7.20 ± 1,88 mmol/L to 6.70 ± 1.38 mmol/L （P = 0.000）, while HbAlc decreased from 7.90 ± 1.78% to 7.60 ± 1.83% （P = 0.000）. Various fixed dose combinations of ramipril/amlodipine were well tolerated and no adverse event related to the use of the medicine has appeared. Conclusions： The fixed dose combination of ramipril/amlodipine was effective in hypertensive diabetic patients who failed to reach target BP previously.
基金supported by the National Natural Science Foundation of China(Grant No.21775017)the Natural Science Foundation of Jilin Province,China(Grant No.20180101174JC)。
文摘We developed a novel portable and automated dissolution test analyzer for rapid and high precision in vitro dissolution testing of drugs.The analyzer consists of a flow-through-cell drug dissolution system,an automated sequential sampling system,a high-speed capillary electrophoresis(HSCE)system,and a data acquisition system.Combining the high-temporal resolution flow-gating sampling approach with HSCE,which has outstanding advantages of efficient separation and resolution,the analyzer can achieve rapid analysis and exhibits the ability in miniaturization for on-site assessment of different active pharmaceutical ingredients.To integrate the flow-through-cell dissolution system with HSCE,a specially designed flow-gating-injection(FGI)interface was employed.The performance of the analyzer was investigated by analyzing the dissolution of immediate-release drugs including single dose(amoxicillin dispersible tablets)and fixed dose combination(amoxicillin and clavulanate potassium)drug tablets with the high-temporal resolutions of 12 s and 20 s,respectively.The dissolution profiles of different active pharmaceutical ingredients could be simultaneously and automatically monitored with high repeatability and accuracy.The analyzer was successfully utilized for the pharmaceutical quality control and bio-relevant dissolution testing,as well as in vivo-in vitro correlation analysis.Our portable analyzer is miniaturized,convenient and of low-cost,and will provide a valuable tool for dissolution testing in pharmaceutical research and development.
