Salvà P, Costa J
Clinical Pharmacology Department, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.
Clin Pharmacokinet. 1995 Sep;29(3):142-53. doi: 10.2165/00003088-199529030-00002.
Zolpidem is an imidazopyridine which differs in structure from the benzodiazepines and zopiclone. It is a strong sedative with only minor anxiolytic, myorelaxant and anticonvulsant properties, and has been shown to be effective in inducing and maintaining sleep in adults. The available evidence suggests that zolpidem produces no rebound or withdrawal effects, and patients have experienced good daytime alertness. Zolpidem 10mg in non-elderly and a reduced dose of 5mg in elderly individuals are clinically effective. In humans, the major metabolic routes include oxidation and hydroxylation; none of the metabolites appears to be pharmacologically active. The pharmacological activity of zolpidem results from selective binding to the central benzodiazepine receptors of the omega 1 subtype. Zolpidem is approximately 92% bound to plasma proteins; absolute bio-availability of zolpidem is about 70%. After single 20mg oral doses, typical values of pharmacokinetic variables for zolpidem in humans are: a peak plasma concentration of 192 to 324 micrograms/L occurring 0.75 to 2.6 hours postdose; a terminal elimination half-line of 1.5 to 3.2 hours; and total clearance of 0.24 to 0.27 ml/min/kg. Zolpidem pharmacokinetics are unchanged during multiple-dose treatment. Zolpidem pharmacokinetics are not significantly influenced by gender. Clearance of zolpidem in children is 3 times higher than in young adults, and is lower in very elderly people. There are no significant differences in the pharmacokinetic parameters between various racial groups. Dosage reduction appears to be prudent in patients with renal disease, and caution should be exercised when prescribing zolpidem to elderly patients with hepatic impairment. Coadministration of haloperidol, cimetidine, ranitidine, chlorpromazine, warfarin, digoxin or flumazenil do not alter the pharmacokinetics of zolpidem; flumazenil predictably antagonises the hypnotic effects of zolpidem. Alertness tends to be reduced when cimetidine is combined with zolpidem. Volunteers treated with imipramine plus zolpidem developed anterograde amnesia.
唑吡坦是一种咪唑并吡啶类药物，其结构与苯二氮䓬类药物和佐匹克隆不同。它是一种强效镇静剂，仅有轻微的抗焦虑、肌松和抗惊厥特性，已被证明对诱导和维持成年人睡眠有效。现有证据表明唑吡坦不会产生反跳或戒断效应，患者白天的警觉性良好。非老年人服用10mg唑吡坦、老年人服用5mg的减量剂量在临床上是有效的。在人体内，主要代谢途径包括氧化和羟基化；没有一种代谢产物具有药理活性。唑吡坦的药理活性源于其对ω1亚型中枢苯二氮䓬受体的选择性结合。唑吡坦与血浆蛋白的结合率约为92%；唑吡坦的绝对生物利用度约为70%。单次口服20mg剂量后，唑吡坦在人体内药代动力学变量的典型值为：给药后0.75至2.6小时出现的血浆峰浓度为192至324微克/升；终末消除半衰期为1.5至3.2小时；总清除率为0.24至0.27毫升/分钟/千克。多次给药治疗期间唑吡坦的药代动力学不变。唑吡坦的药代动力学不受性别的显著影响。儿童体内唑吡坦的清除率比年轻人高3倍，在高龄老人中则较低。不同种族群体之间的药代动力学参数没有显著差异。对于肾病患者，似乎谨慎的做法是减少剂量，给有肝功能损害的老年患者开唑吡坦时应谨慎。同时服用氟哌啶醇、西咪替丁、雷尼替丁、氯丙嗪、华法林、地高辛或氟马西尼不会改变唑吡坦的药代动力学；氟马西尼可预期地拮抗唑吡坦的催眠作用。西咪替丁与唑吡坦合用时警觉性往往会降低。接受丙咪嗪加唑吡坦治疗的志愿者出现了顺行性遗忘。
