Stambaugh J E, Wainer I W, Schwartz I
J Clin Pharmacol. 1978 Oct;18(10):482-90. doi: 10.1002/j.1552-4604.1978.tb01576.x.
Phenobarbital has been observed clinically to alter the metabolism of meperidine, with resultant enhanced toxicity. In order to determine if this effect occurs consistently, 12 health volunteers were entered into a two-way, crossover study comparing the pharmacokinetics and metabolism of meperidine after pretreatment with both phenobarbital and placebo. Phenobarbital pretreatment had no significant effect on serum levels or the half-life of meperidine. However, phenobarbital pretreatment resulted in a decrease in the cumulative excretion of meperidine and an increase in the cumulative excretion of the N-demethylated metabolite normeperidine. Similarly, phenobarbital pretreatment resulted in a decrease in meperidinic acid and increase in normeperidinic acid. In addition, phenobarbital pretreatment also significantly altered the hepatic clearance of meperidine, indicating an increase in the hepatic N-demethylation of meperidine. Since normeperidine has been reported to be less efficacious and more toxic than meperidine, this reported interaction may be important clinically, especially with repeated doses.
临床观察发现苯巴比妥会改变哌替啶的代谢，从而导致毒性增强。为了确定这种效应是否始终存在，12名健康志愿者参与了一项双向交叉研究，比较了苯巴比妥和安慰剂预处理后哌替啶的药代动力学和代谢情况。苯巴比妥预处理对哌替啶的血清水平或半衰期没有显著影响。然而，苯巴比妥预处理导致哌替啶的累积排泄减少，N-去甲基代谢产物去甲哌替啶的累积排泄增加。同样，苯巴比妥预处理导致哌替啶酸减少，去甲哌替啶酸增加。此外，苯巴比妥预处理还显著改变了哌替啶的肝清除率，表明哌替啶的肝脏N-去甲基化增加。由于据报道去甲哌替啶的疗效低于哌替啶且毒性更大，这种报道的相互作用在临床上可能很重要，尤其是在重复给药时。
