Andersson T, Cederberg C, Edvardsson G, Heggelund A, Lundborg P
Research Laboratories, AB Häsle, Mölndal, Sweden.
Clin Pharmacol Ther. 1990 Jan;47(1):79-85. doi: 10.1038/clpt.1990.12.
The effect of omeprazole treatment on diazepam plasma levels was studied in four slow and six rapid metabolizers of omeprazole. Single intravenous doses of diazepam (0.1 mg/kg) were administered after 1 week of oral treatment with omeprazole (20 mg) and placebo. This was a double-blind crossover study with randomized placebo and omeprazole treatments. Blood was collected up to 120 hours after diazepam dosing (still during one-daily omeprazole and placebo administration) for measurement of diazepam and its major metabolite desmethyldiazepam. The slow metabolizers of omeprazole also metabolized diazepam slowly, exhibiting only half the diazepam plasma clearance of the others. The mean clearance of diazepam was decreased 26% after omeprazole in the rapid metabolizers, whereas the slow group showed no apparent interaction. The mean plasma concentrations of desmethyldiazepam showed a more rapid formation in the rapid compared with the slow metabolizers, which is a logical consequence of the rate of diazepam metabolism.
在4名奥美拉唑慢代谢者和6名快代谢者中研究了奥美拉唑治疗对安定血浆水平的影响。在口服奥美拉唑（20毫克）和安慰剂1周后，静脉注射单剂量安定（0.1毫克/千克）。这是一项采用随机安慰剂和奥美拉唑治疗的双盲交叉研究。在安定给药后长达120小时（仍在每日一次的奥美拉唑和安慰剂给药期间）采集血液，用于测定安定及其主要代谢物去甲安定。奥美拉唑的慢代谢者安定代谢也缓慢，其安定血浆清除率仅为其他人的一半。快代谢者中，奥美拉唑治疗后安定的平均清除率降低了26%，而慢代谢组未显示明显相互作用。与慢代谢者相比，快代谢者中去甲安定的平均血浆浓度形成更快，这是安定代谢速率的必然结果。
