Cimetidine impairs nitrazepam clearance.
Cimetidine impairs nitrazepam clearance.
复制标题
西咪替丁会损害硝西泮的清除率。
DOI：
10.1038/clpt.1983.157
复制
发表时间：
1983
影响因子：
6.7
通讯作者：
Abernethy,DR
中科院分区：
文献类型：
--
作者：
Ochs,HR;Greenblatt,DJ;Gugler,R;Müntefering,G;Locniskar,A;Abernethy,DR
在健康受试者中评估了西咪替丁对苯二氮卓衍生物硝西泮肝脏清除率的影响。 6 名患者在无药物状态下接受单次 5 或 10 mg 口服硝西泮剂量，并再次接受治疗剂量的西咪替丁。硝西泮动力学通过每次给药后 72 小时内测量的多个血清浓度来确定。西咪替丁对硝西泮吸收动力学没有影响，因为硝西泮血清峰浓度和峰浓度时间没有改变。西咪替丁不会改变硝西泮的分布容积，但西咪替丁持续降低硝西泮的清除率，从对照组的平均 1.41 ml/min/kg 降至西咪替丁治疗期间的 1.17 ml/min/kg。这导致硝西泮消除 t½ 从 22.2 小时延长至 27.8 小时。因此，西咪替丁在人体内损害药物氧化的能力延伸到了硝西泮的清除能力，硝西泮是一种主要通过硝基还原进行生物转化的化合物。临床药理学和治疗学(1983)34, 227–230; doi:10.1038/clpt.1983.157
The effect of cimetidine on hepatic clearance of the benzodiazepine derivative nitrazepam was evaluated in healthy subjects. Six received a single 5‐ or 10‐mg oral nitrazepam dose in the drug‐free state and again with therapeutic cimetidine doses. Nitrazepam kinetics were determined from multiple serum concentrations measured during the 72 hr after each dose. Cimetidine had no effect on nitrazepam absorption kinetics, since peak serum nitrazepam concentration and time of peak concentration were not altered. Cimetidine did not alter nitrazepam volume of distribution, but cimetidine consistently reduced nitrazepam clearance, from a mean of 1.41 ml/min/kg in the control state to 1.17 ml/min/kg during cimetidine treatment. This resulted in prolongation of nitrazepam elimination t½ from 22.2 to 27.8 hr. Thus the ability of cimetidine to impair drug oxidation in man extends to the capacity for clearance of nitrazepam, a compound biotransformed mainly by nitroreduction.Clinical Pharmacology and Therapeutics(1983)34, 227–230; doi:10.1038/clpt.1983.157