Tremaine L M, Wilner K D, Preskorn S H
Pfizer Central Research, Groton, Connecticut, USA.
Clin Pharmacokinet. 1997;32 Suppl 1:31-6. doi: 10.2165/00003088-199700321-00005.
The effect of the selective serotonin reuptake inhibitor (SSRI) sertraline 200 mg/day on the metabolism of intravenously administered tolbutamide was examined in a randomised nonblinded parallel-group study in 25 healthy male volunteers. There was a small but statistically significant decrease (16%) in the clearance of tolbutamide in patients receiving the maximum recommended dosage of sertraline. The terminal elimination rate constant was also significantly reduced, corresponding to the increase in the terminal elimination half-life (from 6.9 to 8.6 hours). The decrease in clearance was not associated with any significant changes in plasma protein binding or in the apparent volume of distribution of tolbutamide. This suggests that the change in tolbutamide clearance may be due to a slight inhibition of the cytochrome P450 (CYP) isoenzyme CYP2C9/10 when sertraline was administered in its maximum recommended dosage. However, the small changes in the volume of distribution and plasma binding of tolbutamide after sertraline treatment indicate that there is a minimal interaction between sertraline and tolbutamide.
在一项针对25名健康男性志愿者的随机非盲平行组研究中，检测了每天200毫克选择性5-羟色胺再摄取抑制剂（SSRI）舍曲林对静脉注射甲苯磺丁脲代谢的影响。接受最大推荐剂量舍曲林的患者中，甲苯磺丁脲的清除率有小幅但具有统计学意义的下降（16%）。终末消除速率常数也显著降低，这与终末消除半衰期的延长（从6.9小时延长至8.6小时）相对应。清除率的下降与甲苯磺丁脲的血浆蛋白结合或表观分布容积的任何显著变化均无关。这表明，当以最大推荐剂量服用舍曲林时，甲苯磺丁脲清除率的变化可能是由于细胞色素P450（CYP）同工酶CYP2C9/10受到轻微抑制所致。然而，舍曲林治疗后甲苯磺丁脲分布容积和血浆结合的微小变化表明，舍曲林与甲苯磺丁脲之间的相互作用极小。
