Kurtz D L, Bergstrom R F, Goldberg M J, Cerimele B J
Eli Lilly and Company, Lilly Laboratory for Clinical Research, Indianapolis, IN 46202, USA.
Clin Pharmacol Ther. 1997 Aug;62(2):145-56. doi: 10.1016/S0009-9236(97)90062-X.
To examine the pharmacokinetic interaction between the selective serotonin reuptake inhibitor sertraline and the tricyclic antidepressants desipramine or imipramine in 12 healthy male subjects.
Participants received a 50 mg single dose of either desipramine or imipramine under three conditions: alone, after a single 150 mg dose of sertraline, and after the eighth daily 150 mg dose of sertraline. Plasma samples were analyzed for desipramine or imipramine concentration by HPLC with electrochemical detection, and pharmacokinetics were determined with use of noncompartmental analysis of individual data.
Multiple-dose, but not single-dose, treatment with sertraline significantly reduced apparent plasma clearance (CL/F) and prolonged the half-life of desipramine relative to baseline. These changes resulted in higher plasma desipramine concentrations, as indicated by a significant increase in maximum plasma concentration (Cmax) and area under the plasma concentration-time curve extrapolated to infinity [AUC(0-infinity)] (22% and 54%, respectively). Both single- and multiple-dose treatment with sertraline significantly reduced the CL/F of imipramine. This effect was stronger after multiple predoses of sertraline, when imipramine Cmax and AUC(0-infinity) were increased by 39% and 68%, respectively. These treatment effects were consistent between individuals.
This pharmacokinetic interaction is likely the result of an inhibition of CYP2D6 tricyclic metabolism by sertraline. When a tricyclic antidepressant, such as desipramine or imipramine, is coadministered with sertraline, lower dosages of the tricyclic agents may be necessary to prevent elevated tricyclic levels.
在12名健康男性受试者中研究选择性5-羟色胺再摄取抑制剂舍曲林与三环类抗抑郁药地昔帕明或丙咪嗪之间的药代动力学相互作用。
受试者在三种情况下接受50mg单剂量的地昔帕明或丙咪嗪：单独服用、在单次服用150mg舍曲林后以及在每日服用150mg舍曲林八次后。通过高效液相色谱电化学检测分析血浆样本中地昔帕明或丙咪嗪的浓度，并使用个体数据的非房室分析确定药代动力学。
与基线相比，舍曲林多剂量而非单剂量治疗显著降低了地昔帕明的表观血浆清除率（CL/F）并延长了其半衰期。这些变化导致血浆地昔帕明浓度升高，最大血浆浓度（Cmax）和外推至无穷大的血浆浓度-时间曲线下面积[AUC(0-无穷大)]分别显著增加22%和54%。舍曲林单剂量和多剂量治疗均显著降低了丙咪嗪的CL/F。在舍曲林多次预给药后这种作用更强，此时丙咪嗪的Cmax和AUC(0-无穷大)分别增加了39%和68%。这些治疗效果在个体之间是一致的。
这种药代动力学相互作用可能是舍曲林抑制CYP2D6三环类代谢的结果。当三环类抗抑郁药如地昔帕明或丙咪嗪与舍曲林合用时，可能需要降低三环类药物的剂量以防止三环类药物水平升高。
