Teunissen M W, Wahlén A, Vinnars E, Breimer D D
Eur J Clin Pharmacol. 1984;27(4):447-52. doi: 10.1007/BF00549593.
Alaproclate, a selective serotonin reuptake inhibitor, presently undergoing clinical trial for the treatment of major depressive disorders, has been shown to inhibit hexobarbital metabolism in mice. In the present study the influence of oral alaproclate on the total plasma clearance of antipyrine and on the formation of its metabolites was investigated in 10 healthy volunteers. The peak level of alaproclate was reached after about 1.5 h, and after a distribution phase, its plasma elimination half-life was between 3.0 and 3.5 h. Antipyrine tests were performed before treatment, during the first four doses and after the seventh dose of alaproclate 200 mg/day. During treatment, total plasma antipyrine clearance and the clearance for production of all antipyrine metabolites were reduced by 30%, indicating non-selective inhibition of oxidative drug-metabolizing enzyme activity in man by alaproclate. After the last dose of alaproclate, antipyrine plasma clearance and the clearance to its metabolites returned to control values. In order to allow more detailed evaluation of the results, the time course of the clearances for production of metabolites was investigated. This revealed that the extent of inhibition of metabolite formation by alaproclate was dependent on the plasma alaproclate level, indicating a rapidly reversible inhibition.
阿那普明，一种选择性5-羟色胺再摄取抑制剂，目前正处于治疗重度抑郁症的临床试验阶段，已被证明可抑制小鼠体内己巴比妥的代谢。在本研究中，对10名健康志愿者研究了口服阿那普明对安替比林总血浆清除率及其代谢物形成的影响。阿那普明在约1.5小时后达到峰值水平，经过分布期后，其血浆消除半衰期在3.0至3.5小时之间。在治疗前、阿那普明200毫克/天的前四剂给药期间以及第七剂给药后进行了安替比林试验。治疗期间，总血浆安替比林清除率以及所有安替比林代谢物生成的清除率降低了30%，表明阿那普明对人体氧化药物代谢酶活性具有非选择性抑制作用。在最后一剂阿那普明给药后，安替比林血浆清除率及其代谢物清除率恢复到对照值。为了更详细地评估结果，对代谢物生成清除率的时间进程进行了研究。结果表明，阿那普明对代谢物形成的抑制程度取决于血浆阿那普明水平，表明存在快速可逆性抑制。
