Benzodiazepine hypnotic metabolism: drug interactions and clinical implications.
Benzodiazepine hypnotic metabolism: drug interactions and clinical implications.
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苯二氮卓催眠代谢：药物相互作用和临床意义。
DOI：
10.1111/j.1600-0447.1986.tb08977.x
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Shader,RI
中科院分区：
文献类型：
--
作者：
Abernethy,DR;Greenblatt,DJ;Shader,RI
苯二氮卓类药物是催眠治疗的首选药物。尽管该类药物在中枢神经系统中的苯二氮卓类药物作用机制相似，但吸收和消除途径的差异与观察到的临床效应差异相关。单次给药后，催眠作用的起效与药物吸收率最密切相关，作用持续时间与药物分布程度更密切相关。单个苯二氮卓类药物对中枢神经系统特定结合位点的相对亲和力也可决定作用持续时间。在多次给药慢性治疗期间，代谢生物转化途径和消除半衰期更为重要。在老年人和中枢神经系统缺陷或慢性肝病患者中，可观察到由于高剂量苯二氮卓类药物蓄积导致的药物不良反应发生率增加。苯二氮卓代谢生物转化和清除分为三组。第1组-氧化生物转化;第2组-高清除率药物;第3组-药物偶联。第1组和第2组涉及许多药物-疾病和药物-药物相互作用。第3组药物在肝病患者中或与药物生物转化抑制剂一起给药时几乎没有变化。这些代谢相互作用的临床意义是可变的，但抑制组1和组2苯二氮卓类药物清除与镇静和精神损害增加相关。
Benzodiazepines are the drugs of choice when initiating hypnotic therapy. Though the mechanism of benzodiazepine action in the central nervous system is similar for all drugs in this class, differences in absorption and pathway of elimination are associated with differences in observed clinical effect. After single‐dose administration, onset of hypnotic effect is most closely related to rate of drug absorption and duration of effect is more closely associated with extent of drug distribution. Relative affinity of the individual benzodiazepine for the specific central nervous system binding site may also determine duration of action. During multiple‐dose chronic therapy, route of metabolic biotransformation and elimination half‐life assume more importance. An increased incidence of adverse drug effects due to high doses of accumulating benzodiazepines may be seen in the elderly and patients with central nervous system deficits or chronic liver disease. Benzodiazepine metabolic biotransformation and clearance is broken into three groups. Group 1—oxidative biotransformation; Group 2—high clearance drugs; Group 3—drug conjugation. Groups 1 and 2 are implicated in a number of drug‐disease and drug‐drug interactions. Group 3 drugs have little change in patients with liver disease or when administered with inhibitors of drug biotransformation. Clinical implications of these metabolic interactions are variable, but inhibition of Group 1 and 2 benzodiazepine clearance has been associated with increased sedation and psychomotor impairment.