In the present study, we aimed to investigate the effect of CYP3A4＊ 18 genotype on the pharmacokinetics of zolpidem in healthy Chinese Hui volunteers. Blood samples were collected from volunteers for CYP3A4 genotypin...In the present study, we aimed to investigate the effect of CYP3A4＊ 18 genotype on the pharmacokinetics of zolpidem in healthy Chinese Hui volunteers. Blood samples were collected from volunteers for CYP3A4 genotyping using a polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） assay. A pharmacokinetic study was then carried out in three groups with CYP3A4＊1/＊1 （n = 6）, CYP3A4＊1/＊18 （n = 6） and CYP3A4＊18/＊18 （n = 6） genotypes. Plasma levels of zolpidem were determined by HPLC-FLD method before and after a single oral dose of 10 mg zolpidem tartrate tablet. Significant differences were observed in the pharmacokinetic parameters of zolpidem among the three genotype groups （P〈0.05）. Compared with the CYP3A4＊1/＊1 group, the Cm,x of zolpidem in ＊1/＊18 and ＊18/＊18 groups （mean, 95% CI） was 0.89 （0.65-1.12） and 0.57 （0.47-0.66）, respectively, and the AUC0-1 in the ＊1/＊18 and ＊18/＊18 groups （mean, 95% CI） was 0.74 （0.22-1.26） and 0.61 （0.24-0.98）, respectively. There was a significant trend towards lower Cmax and AUC0-1 values of zolpidem in individuals with more CYP3A＊ 18 alleles, suggesting a gene-dosage effect. The study demonstrated that the CYP3A4＊ 18 allele played an important role in the pharmacokinetics of the zolpidem after oral administration.展开更多
Zolpidem is a short-acting non-benzodiazepine hypnotic agent,commonly recommended for short-term treatment of insomnia.Zolpidem has less dependence potential than benzodiazepines.Patients with mental illnesses often h...Zolpidem is a short-acting non-benzodiazepine hypnotic agent,commonly recommended for short-term treatment of insomnia.Zolpidem has less dependence potential than benzodiazepines.Patients with mental illnesses often have disturbed sleep,for which zolpidem is often prescribed.Long-term use and self-medication(in more than recommended doses)are more likely to cause dependence.We report here a case of bipolar affective disorder with epilepsy,who developed dependence to zolpidem and had severe withdrawal symptoms.The management issues are also discussed with review of the literature.展开更多
Insomnia and related sleep disorders (somnipathies) affect a large segment of the population, and result in a significant negative impact on quality of life and reduced or lost productivity. The speed of sleep onset i...Insomnia and related sleep disorders (somnipathies) affect a large segment of the population, and result in a significant negative impact on quality of life and reduced or lost productivity. The speed of sleep onset is a critical characteristic of successful pharmacotherapeutic intervention for insomnia. Zolpidem, a non-benzodiazepine benzodiazepine receptor agonist (nBzRA) is widely used to treat insomnia. Although not itself a benzodiazepine (BZD), zolpidem has high binding affinity for the benzodiazepine receptor, which acts as a positive allosteric modulator of the GABAA receptor complex. It therefore increases the neuronal transmembrane influx of Cl- ions, thereby decreasing neuronal excitability and promoting sleep. In this four-way crossover, dose-ranging, multiple-treatment study, a lingual spray formulation of zolpidem was safe and well-tolerated and yielded more rapid pharmacokinetics (mean plasma concentration) and efficacy (visual analog scale and digit symbol substitution test) compared to oral tablets.展开更多
Zolpidem is a sedative-hypnotic drug used to treat in sleep disorders, and it is the most commonly prescribed drug for insomnia. It reduces sleep latency and increases total sleep time. However, some studies have repo...Zolpidem is a sedative-hypnotic drug used to treat in sleep disorders, and it is the most commonly prescribed drug for insomnia. It reduces sleep latency and increases total sleep time. However, some studies have reported that zolpidem might induce sleep related eating disorder (SRED). SRED is characterized by recurrent episodes of compulsive and involuntary eating during night sleep, accompanied by partial consciousness and limited subsequent recall. The pathophysiology of SRED is unknown. Patients with SRED usually suffer from other sleep disorders such as sleepwalking, restless legs syndrome, and obstructive sleep apnea. In this article, we present an overview of case reports on SRED induced by zolpidem.展开更多
To examine the efficacy of the melatonin receptor agonist ramelteon for nocturia, it was compared with zolpidem, a conventional non-benzodiazepine hypnotic. A total of 50 patients with nocturia (32 urinations/night) w...To examine the efficacy of the melatonin receptor agonist ramelteon for nocturia, it was compared with zolpidem, a conventional non-benzodiazepine hypnotic. A total of 50 patients with nocturia (32 urinations/night) were enrolled. Subjects assigned odd numbers or even numbers were respectively prescribed 8 mg of ramelteon (n = 27;mean age: 75 years) or 5 mg of zolpidem (n = 23;mean age: 73 years) once a day before sleeping for 4 weeks. The daytime and nighttime frequencies of urination, as well as the results of global self-assessment by the patients, were compared between the two groups before and after 4 weeks of treatment. Both ramelteon and zolpidem caused a significant decrease of nocturia to about once per night after 4 weeks. The global self-assessment rating at 4 weeks was “good” or “fair” for more patients in the zolpidem group than in the ramelteon group, while the rating was “excellent” or “no change” for more patients in the ramelteon group. There were no serious adverse events in either group. Ramelteon was safe and effective for nocturia, achieving similar results to zolpidem. However, responders and non-responders to ramelteon were more clearly distinguished. Ramelteon might be effective for patients with sleep disturbance and nocturia because of low melatonin levels. Therefore, as diagnostic therapy for identification of nocturia caused by sleep disturbance and melatonin deficiency, ramelteon should be administered to patients who do not respond to alpha-1 antagonists and/or anticholinergic agents.展开更多
Zolpidem, as an imidazopyridine agent, is a widely prescribed drug among practitioners for short-term treatment of insomnia. Nevertheless, there have been a number of cases associated with the adverse effects of the s...Zolpidem, as an imidazopyridine agent, is a widely prescribed drug among practitioners for short-term treatment of insomnia. Nevertheless, there have been a number of cases associated with the adverse effects of the stated drug recently. Many cases of serious complications induced by high dose of zolpidem have been reported. Further to the existing reports of adverse reactions to zolpidem, throughout the current manuscript, another case of zolpidem-induced loss of consciousness is going to be presented. The case had taken 100 mg of zolpidem and afterwards, went into an unknown status of narcolepsy, faint, seizure or transient coma. Overdosing zolpidem and being affected by its central effects, he performed risky actions such as cooking by a gas oven and eating meal while intoxicated. The current case suggests that zolpidem overdose might contribute to loss of consciousness and exhibition of high-risk behaviors.展开更多
The objective of this study was to evaluate the difference in the pharmacokinetics of zolpidem tatrate in subjects from five Chinese ethnicities(Han,Mongolian,Uigur,Korean and Hui).Healthy subjects(10 Hans,10 Mongolia...The objective of this study was to evaluate the difference in the pharmacokinetics of zolpidem tatrate in subjects from five Chinese ethnicities(Han,Mongolian,Uigur,Korean and Hui).Healthy subjects(10 Hans,10 Mongolians,10 Uigurs,10 Koreans and 9 Huis)were recruited and each received a 10 mg tablet-dose of zolpidem tatrate.A total of 12 plasma samples were collected over a 12 h period after administration.The concentrations of zolpidem in plasma were determined by an HPLC-FLU method,after which the pharmacokinetic parameters were determined using DAS 2.0 software and analyzed by SPSS 16.0 software.After normalization by weight,no differences were noted in the pharmacokinetic parameters of zolpidem tatrate among the five ethnic groups(P>0.05).However,there were statistically significant differences between males and females for the pharmacokinetic parameters(P<0.05).The metabolism of zolpidem tatrate in males was faster than in females.Results indicate that ethnicity has no significant impact on the pharmacokinetics of zolpidem tatrate after a single oral dose in healthy Chinese subjects.However,an effect of gender on the pharmacokinetics of zolpidem tatrate can be noted.展开更多
基金Funds of the Chinese Army Medical Science and Technology Research"Eleventh Five-Year Plan"Project(Grant No.06G023)
文摘In the present study, we aimed to investigate the effect of CYP3A4＊ 18 genotype on the pharmacokinetics of zolpidem in healthy Chinese Hui volunteers. Blood samples were collected from volunteers for CYP3A4 genotyping using a polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） assay. A pharmacokinetic study was then carried out in three groups with CYP3A4＊1/＊1 （n = 6）, CYP3A4＊1/＊18 （n = 6） and CYP3A4＊18/＊18 （n = 6） genotypes. Plasma levels of zolpidem were determined by HPLC-FLD method before and after a single oral dose of 10 mg zolpidem tartrate tablet. Significant differences were observed in the pharmacokinetic parameters of zolpidem among the three genotype groups （P〈0.05）. Compared with the CYP3A4＊1/＊1 group, the Cm,x of zolpidem in ＊1/＊18 and ＊18/＊18 groups （mean, 95% CI） was 0.89 （0.65-1.12） and 0.57 （0.47-0.66）, respectively, and the AUC0-1 in the ＊1/＊18 and ＊18/＊18 groups （mean, 95% CI） was 0.74 （0.22-1.26） and 0.61 （0.24-0.98）, respectively. There was a significant trend towards lower Cmax and AUC0-1 values of zolpidem in individuals with more CYP3A＊ 18 alleles, suggesting a gene-dosage effect. The study demonstrated that the CYP3A4＊ 18 allele played an important role in the pharmacokinetics of the zolpidem after oral administration.
文摘Zolpidem is a short-acting non-benzodiazepine hypnotic agent,commonly recommended for short-term treatment of insomnia.Zolpidem has less dependence potential than benzodiazepines.Patients with mental illnesses often have disturbed sleep,for which zolpidem is often prescribed.Long-term use and self-medication(in more than recommended doses)are more likely to cause dependence.We report here a case of bipolar affective disorder with epilepsy,who developed dependence to zolpidem and had severe withdrawal symptoms.The management issues are also discussed with review of the literature.
文摘Insomnia and related sleep disorders (somnipathies) affect a large segment of the population, and result in a significant negative impact on quality of life and reduced or lost productivity. The speed of sleep onset is a critical characteristic of successful pharmacotherapeutic intervention for insomnia. Zolpidem, a non-benzodiazepine benzodiazepine receptor agonist (nBzRA) is widely used to treat insomnia. Although not itself a benzodiazepine (BZD), zolpidem has high binding affinity for the benzodiazepine receptor, which acts as a positive allosteric modulator of the GABAA receptor complex. It therefore increases the neuronal transmembrane influx of Cl- ions, thereby decreasing neuronal excitability and promoting sleep. In this four-way crossover, dose-ranging, multiple-treatment study, a lingual spray formulation of zolpidem was safe and well-tolerated and yielded more rapid pharmacokinetics (mean plasma concentration) and efficacy (visual analog scale and digit symbol substitution test) compared to oral tablets.
文摘Zolpidem is a sedative-hypnotic drug used to treat in sleep disorders, and it is the most commonly prescribed drug for insomnia. It reduces sleep latency and increases total sleep time. However, some studies have reported that zolpidem might induce sleep related eating disorder (SRED). SRED is characterized by recurrent episodes of compulsive and involuntary eating during night sleep, accompanied by partial consciousness and limited subsequent recall. The pathophysiology of SRED is unknown. Patients with SRED usually suffer from other sleep disorders such as sleepwalking, restless legs syndrome, and obstructive sleep apnea. In this article, we present an overview of case reports on SRED induced by zolpidem.
文摘To examine the efficacy of the melatonin receptor agonist ramelteon for nocturia, it was compared with zolpidem, a conventional non-benzodiazepine hypnotic. A total of 50 patients with nocturia (32 urinations/night) were enrolled. Subjects assigned odd numbers or even numbers were respectively prescribed 8 mg of ramelteon (n = 27;mean age: 75 years) or 5 mg of zolpidem (n = 23;mean age: 73 years) once a day before sleeping for 4 weeks. The daytime and nighttime frequencies of urination, as well as the results of global self-assessment by the patients, were compared between the two groups before and after 4 weeks of treatment. Both ramelteon and zolpidem caused a significant decrease of nocturia to about once per night after 4 weeks. The global self-assessment rating at 4 weeks was “good” or “fair” for more patients in the zolpidem group than in the ramelteon group, while the rating was “excellent” or “no change” for more patients in the ramelteon group. There were no serious adverse events in either group. Ramelteon was safe and effective for nocturia, achieving similar results to zolpidem. However, responders and non-responders to ramelteon were more clearly distinguished. Ramelteon might be effective for patients with sleep disturbance and nocturia because of low melatonin levels. Therefore, as diagnostic therapy for identification of nocturia caused by sleep disturbance and melatonin deficiency, ramelteon should be administered to patients who do not respond to alpha-1 antagonists and/or anticholinergic agents.
文摘Zolpidem, as an imidazopyridine agent, is a widely prescribed drug among practitioners for short-term treatment of insomnia. Nevertheless, there have been a number of cases associated with the adverse effects of the stated drug recently. Many cases of serious complications induced by high dose of zolpidem have been reported. Further to the existing reports of adverse reactions to zolpidem, throughout the current manuscript, another case of zolpidem-induced loss of consciousness is going to be presented. The case had taken 100 mg of zolpidem and afterwards, went into an unknown status of narcolepsy, faint, seizure or transient coma. Overdosing zolpidem and being affected by its central effects, he performed risky actions such as cooking by a gas oven and eating meal while intoxicated. The current case suggests that zolpidem overdose might contribute to loss of consciousness and exhibition of high-risk behaviors.
基金This research work was supported financially by the Entire Armed Forces“11th 5-year plan”Medicine Health Science and Technology Attach Topic(06G023).
文摘The objective of this study was to evaluate the difference in the pharmacokinetics of zolpidem tatrate in subjects from five Chinese ethnicities(Han,Mongolian,Uigur,Korean and Hui).Healthy subjects(10 Hans,10 Mongolians,10 Uigurs,10 Koreans and 9 Huis)were recruited and each received a 10 mg tablet-dose of zolpidem tatrate.A total of 12 plasma samples were collected over a 12 h period after administration.The concentrations of zolpidem in plasma were determined by an HPLC-FLU method,after which the pharmacokinetic parameters were determined using DAS 2.0 software and analyzed by SPSS 16.0 software.After normalization by weight,no differences were noted in the pharmacokinetic parameters of zolpidem tatrate among the five ethnic groups(P>0.05).However,there were statistically significant differences between males and females for the pharmacokinetic parameters(P<0.05).The metabolism of zolpidem tatrate in males was faster than in females.Results indicate that ethnicity has no significant impact on the pharmacokinetics of zolpidem tatrate after a single oral dose in healthy Chinese subjects.However,an effect of gender on the pharmacokinetics of zolpidem tatrate can be noted.
