Rapeport W G, Coates P E, Dewland P M, Forster P L
Pfizer Central Research, Sandwich, Kent, United Kingdom.
J Clin Psychiatry. 1996;57 Suppl 1:16-9.
The effects of oral administration of sertraline on the plasma concentration profile and renal clearance of digoxin were assessed in 20 healthy male subjects in a double-blind, randomized study.
All subjects first received digoxin 0.5 mg twice daily on Day 1, 0.25 mg twice daily on Day 2, and 0.25 mg daily thereafter. On Day 11, 10 subjects began concomitant sertraline administration with an initial dose of 50 mg/day that was titrated upward over 7 days to 200 mg/day, which was given over the remainder of the study period. The other 10 subjects received concomitant digoxin and placebo for 17 days beginning on Day 11. Trough plasma concentrations of digoxin were monitored daily beginning on Day 7. Blood samples and 24-hour urine collections were used to determine steady-state digoxin concentration and renal clearance before, during, and after sertraline coadministration.
Sertraline had no effect on digoxin pharmacokinetics, except for a decrease in the time to reach the maximum plasma digoxin concentration (Tmax) compared with placebo (p = .0046), a finding thought to be of limited clinical significance. Side effects of mild-to-moderate severity were reported by 5 of 10 sertraline-treated subjects and by 6 of 10 placebo-treated subjects.
The results of this study suggest that dosing adjustments of digoxin may not be necessary in patients receiving concomitant sertraline administration.
在一项双盲、随机研究中，对20名健康男性受试者评估了口服舍曲林对地高辛血浆浓度曲线和肾清除率的影响。
所有受试者在第1天先接受每日两次0.5mg地高辛，第2天每日两次0.25mg，此后每日0.25mg。在第11天，10名受试者开始同时服用舍曲林，初始剂量为50mg/天，在7天内逐渐增加至200mg/天，并在研究剩余期间维持该剂量。另外10名受试者从第11天开始同时服用地高辛和安慰剂，持续17天。从第7天开始每日监测地高辛的谷浓度。在舍曲林联合给药前、给药期间和给药后，采集血样和24小时尿液样本以测定地高辛的稳态浓度和肾清除率。
舍曲林对地高辛的药代动力学没有影响，不过与安慰剂相比，达到地高辛最大血浆浓度的时间（Tmax）有所缩短（p = 0.0046），这一发现被认为临床意义有限。10名接受舍曲林治疗的受试者中有5人报告了轻至中度的副作用，10名接受安慰剂治疗的受试者中有6人报告了副作用。
本研究结果表明，接受舍曲林联合给药的患者可能无需调整地高辛的剂量。
