Ronfeld R A, Tremaine L M, Wilner K D
Pfizer Central Research, Groton, Connecticut, USA.
Clin Pharmacokinet. 1997;32 Suppl 1:22-30. doi: 10.2165/00003088-199700321-00004.
A nonblinded study was conducted to compare the pharmacokinetic properties of the selective serotonin reuptake inhibitor sertraline in 22 young (aged 18 to 45 years) and 22 elderly (> 65 years) volunteers, of whom half were male and half were female. In this study, sertraline was administered at a dosage of 200mg once daily (the maximum recommended daily dosage) for 21 days after upward dosage titration from 50 mg/day over a 9-day period. Thus, this study was designed to measure the effect of age and gender on the pharmacokinetic properties of sertraline at the maximum dosage recommended for clinical use. The terminal elimination half-life (t1/2 beta ) of sertraline was similar in young females, elderly males and elderly females (mean t1/2 beta ranged from 32.1 to 36.7 hours in these groups) but shorter (22.4 hours) in the young males. The mean maximum plasma sertraline concentration (Cmax) and the mean steady-state area under the plasma concentration-time curve from time zero to 24 hours postdose (AUC24) were also similar between the young females, elderly males and elderly females, but were approximately 25% lower in the young males. The time to Cmax was unaffected by age or gender and ranged from 6.4 to 6.9 hours. N-Demethylsertraline is the principal metabolite of sertraline and does not contribute significantly to its serotonergic actions. The mean values for N-demethylsertraline trough plasma concentrations, AUC24 and Cmax were comparable in elderly males and females and young females but lower in young males. The ratios of mean AUC24 and Cmax for N-demethylsertraline to the AUC24 and Cmax for sertraline were similar between the 4 groups.
开展了一项非盲法研究，以比较选择性5-羟色胺再摄取抑制剂舍曲林在22名年轻（18至45岁）志愿者和22名老年（>65岁）志愿者中的药代动力学特性，其中一半为男性，一半为女性。在本研究中，舍曲林在9天内从50mg/天向上滴定剂量后，以200mg/天的剂量（最大推荐日剂量）每日给药一次，持续21天。因此，本研究旨在测量年龄和性别对舍曲林在临床使用推荐最大剂量下药代动力学特性的影响。舍曲林的终末消除半衰期（t1/2β）在年轻女性、老年男性和老年女性中相似（这些组的平均t1/2β范围为32.1至36.7小时），但在年轻男性中较短（22.4小时）。年轻女性、老年男性和老年女性之间的平均最大血浆舍曲林浓度（Cmax）以及给药后0至24小时血浆浓度-时间曲线下的平均稳态面积（AUC24）也相似，但在年轻男性中约低25%。达到Cmax的时间不受年龄或性别的影响，范围为6.4至6.9小时。N-去甲基舍曲林是舍曲林的主要代谢产物，对其5-羟色胺能作用没有显著贡献。老年男性和女性以及年轻女性中N-去甲基舍曲林谷血浆浓度、AUC24和Cmax的平均值相当，但在年轻男性中较低。4组中N-去甲基舍曲林的平均AUC24和Cmax与舍曲林的AUC24和Cmax之比相似。
