The Impact of Sertraline Co-Administration on the Pharmacokinetics of Olanzapine: A Population Pharmacokinetic Analysis of the STOP-PD

被引：15

作者：

Davies, Simon J. C. ^{[1
,2
]}

Mulsant, Benoit H. ^{[1
,2
]}

Flint, Alastair J. ^{[2
,3
]}

Meyers, Barnett S. ^{[4
,5
]}

Rothschild, Anthony J. ^{[6
,7
]}

Whyte, Ellen M. ^{[8
]}

Kirshner, Margaret M. ^{[9
]}

Sorisio, Denise ^{[8
]}

Pollock, Bruce G. ^{[1
,2
]}

Bies, Robert R. ^{[1
,10
,11
]}

机构：

[1] Ctr Addict & Mental Hlth, Toronto, ON M6J 1H4, Canada

[2] Univ Toronto, Dept Psychiat, Toronto, ON, Canada

[3] Univ Hlth Network, Dept Psychiat, Toronto, ON, Canada

[4] Cornell Univ, Weill Med Coll, New York, NY 10021 USA

[5] New York Presbyterian Hosp, New York, NY USA

[6] Univ Massachusetts, Sch Med, Worcester, MA USA

[7] Univ Massachusetts, Mem Hlth Care, Worcester, MA 01605 USA

[8] Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA USA

[9] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA

[10] Ctr Addict & Mental Hlth, Campbell Family Mental Hlth Res Inst, Toronto, ON, Canada

[11] Indiana Clin & Translat Sci Inst, Indianapolis, IN USA

来源：

CLINICAL PHARMACOKINETICS | 2015年 / 54卷 / 11期

关键词：

DRUG-MONITORING-SERVICE; PSYCHOTIC DEPRESSION; ANTIDEPRESSANTS; FEATURES; PROFILE;

D O I：

10.1007/s40262-015-0275-1

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Background and Objective Clinical evidence and expert opinion support using a combination of an antipsychotic and an antidepressant when treating major depression with psychotic features. We characterized the impact of sertraline co-administration on olanzapine clearance in psychotic depression using population pharmacokinetic methods. Methods The Study of Pharmacotherapy for Psychotic Depression (STOP-PD) randomized 259 participants to olanzapine plus placebo or olanzapine plus sertraline. Olanzapine was started at 2.5-5 mg/day and sertraline at 25-50 mg/day. Doses were increased to a maximum of 20 mg/day for olanzapine and 200 mg/day for sertraline. Up to four olanzapine concentration samples were collected during the 12-week trial and 12-week continuation phase. We used NONMEM (Version VII) for population pharmacokinetic analysis, assessing effects of the covariates sex, African American origin, smoking, age, and sertraline co-administration. Results Population pharmacokinetic analysis comprised 336 samples from 175 individuals. The structural model published by Bigos et al. was sufficient to describe the olanzapine data adequately: a one-compartment model with first-order absorption and elimination, using an additive residual error structure with the absorption rate constant fixed to 0.5. Sertraline co-administration significantly increased olanzapine apparent clearance (p < 0.005) by 25-35 % depending on the patient characteristics included. Male sex was associated with a significantly increased clearance. Age and race did not have a significant impact on clearance. Conclusions Contrary to expectations from the knowledge of cytochrome P450 interactions, sertraline increased olanzapine apparent clearance. Plausible explanations include patients treated with sertraline having poorer adherence to olanzapine, or the impact of sertraline inhibition of transporters resulting in increased intracellular concentrations and thus access to metabolizing enzymes.

引用

页码：1161 / 1168

页数：8