The effect of sertraline on the pharmacokinetics of desipramine and imipramine

被引:49
作者
Kurtz, DL
Bergstrom, RF
Goldberg, MJ
Cerimele, BJ
机构
[1] ELI LILLY & CO,LILLY RES LABS,LILLY LAB CLIN RES,INDIANAPOLIS,IN 46202
[2] INDIANA UNIV,WISHARD MEM HOSP,INDIANAPOLIS,IN 46202
关键词
D O I
10.1016/S0009-9236(97)90062-X
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Objective: To examine the pharmacokinetic interaction between the selective serotonin reuptake inhibitor sertraline and the tricyclic antidepressants desipramine or imipramine in 12 healthy male subjects. Methods: 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. Results: 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 (C-max) 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 C-max and AUC(0-infinity) were increased by 39% and 68%, respectively. These treatment effects were consistent between individuals. Conclusions: 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.
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页码:145 / 156
页数:12
相关论文
共 36 条
[1]  
[Anonymous], SAS STAT US GUID VER
[2]  
BARROS J, 1993, AM J PSYCHIAT, V150, P1751
[3]  
*BAS AN, STAND AN PROT 820019
[4]   FLUOXETINE INDUCES ELEVATION OF DESIPRAMINE LEVEL AND EXACERBATION OF GERIATRIC NONPSYCHOTIC DEPRESSION [J].
BELL, IR ;
COLE, JO .
JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY, 1988, 8 (06) :447-448
[5]   QUANTIFICATION AND MECHANISM OF THE FLUOXETINE AND TRICYCLIC ANTIDEPRESSANT INTERACTION [J].
BERGSTROM, RF ;
PEYTON, AL ;
LEMBERGER, L .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1992, 51 (03) :239-248
[6]   THE INFLUENCE OF ENVIRONMENTAL AND GENETIC-FACTORS ON CYP2D6, CYP1A2 AND UDP-GLUCURONOSYLTRANSFERASES IN MAN USING SPARTEINE, CAFFEINE, AND PARACETAMOL AS PROBES [J].
BOCK, KW ;
SCHRENK, D ;
FORSTER, A ;
GRIESE, EU ;
MORIKE, K ;
BROCKMEIER, D ;
EICHELBAUM, M .
PHARMACOGENETICS, 1994, 4 (04) :209-218
[7]  
BOYER WF, 1991, SELECTIVE SEROTONIN, P81
[8]   INHIBITION BY PAROXETINE OF DESIPRAMINE METABOLISM IN EXTENSIVE BUT NOT IN POOR METABOLIZERS OF SPARTEINE [J].
BROSEN, K ;
HANSEN, JG ;
NIELSEN, KK ;
SINDRUP, SH ;
GRAM, LF .
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 1993, 44 (04) :349-355
[9]   FLUVOXAMINE IS A POTENT INHIBITOR OF CYTOCHROME-P4501A2 [J].
BROSEN, K ;
SKJELBO, E ;
RASMUSSEN, BB ;
POULSEN, HE ;
LOFT, S .
BIOCHEMICAL PHARMACOLOGY, 1993, 45 (06) :1211-1214
[10]   1ST-PASS METABOLISM OF IMIPRAMINE AND DESIPRAMINE - IMPACT OF THE SPARTEINE OXIDATION PHENOTYPE [J].
BROSEN, K ;
GRAM, LF .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1988, 43 (04) :400-406