Cho A K, Hiramatsu M, Pechnick R N, Di Stefano E
Department of Pharmacology, University of California, Los Angeles School of Medicine.
J Pharmacol Exp Ther. 1989 Jul;250(1):210-5.
The role of metabolism in the in vivo actions of phencyclidine (PCP) was examined by comparing deuterium-substituted drug with drug of normal isotopic abundance. PCP elicits two responses that differ in their time course, ataxia, which is observable immediately after dosage, and hypothermia, which peaks approximately 90 to 120 min after drug administration. The role of metabolism in these responses was determined by comparing bioavailabilities of deuterium enriched (d10) and normal (d0) PCP with the two responses. Plasma concentration was determined after the i.v. and i.p. administration of d10 and d0 drug and the bioavailability of the d10 was found to be 1.3 to 1.5 times the d0. The clearance of the d10 was also smaller than the d0. The d10, which is pharmacologically equivalent in vitro, is metabolized more slowly than the d0 in vitro. The pharmacokinetic and pharmacodynamic bioavailabilities exhibited comparable isotope effects, indicating that both responses are due to the actions of the parent drug.
通过比较氘取代药物与具有正常同位素丰度的药物，研究了代谢在苯环己哌啶（PCP）体内作用中的作用。PCP引发两种时间进程不同的反应，即共济失调，给药后立即可见，以及体温过低，给药后约90至120分钟达到峰值。通过比较富含氘（d10）和正常（d0）PCP对这两种反应的生物利用度，确定了代谢在这些反应中的作用。静脉注射和腹腔注射d10和d0药物后测定血浆浓度，发现d10的生物利用度是d0的1.3至1.5倍。d10的清除率也低于d0。在体外药理等效的d10在体外比d0代谢更慢。药代动力学和药效学生物利用度表现出相当的同位素效应，表明这两种反应均归因于母体药物的作用。
