EFFECT OF FLUVOXAMINE ON THE PHARMACOKINETICS OF IMIPRAMINE AND DESIPRAMINE IN HEALTHY-SUBJECTS

被引:111
作者
SPINA, E [1 ]
POLLICINO, AM [1 ]
AVENOSO, A [1 ]
CAMPO, GM [1 ]
PERUCCA, E [1 ]
CAPUTI, AP [1 ]
机构
[1] UNIV PAVIA,CLIN PHARMACOL UNIT,I-27100 PAVIA,ITALY
关键词
FLUVOXAMINE; IMIPRAMINE; DESIPRAMINE; DRUG INTERACTION; DEMETHYLATION; HYDROXYLATION;
D O I
10.1097/00007691-199306000-00011
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
The effect of the selective serotonin reuptake inhibitor fluvoxamine (100 mg/day for 10 consecutive days) on the kinetics of a single oral dose of imipramine (50 mg) and desipramine (100 mg) was investigated in 12 healthy subjects. Compared with a control session, treatment with fluvoxamine caused a significant prolongation of imipramine half-life (from 22.8 +/- 6.4 to 40.5 +/- 5.0 h, means +/- SD, p < 0.01) and a marked decrease in imipramine apparent oral clearance (from 1.02 +/- 0.19 to 0.28 +/- 0.06 L/h/kg, p < 0.0001). No significant changes in desipramine kinetics were observed during fluvoxamine treatment. These findings indicate that, at the dosage tested, fluvoxamine markedly inhibits the demethylation of imipramine without affecting significantly the CYP2D6-mediated hydroxylation of desipramine.
引用
收藏
页码:243 / 246
页数:4
相关论文
共 22 条
[1]  
ARANOW RB, 1989, AM J PSYCHIAT, V146, P911
[2]   FLUVOXAMINE - A REVIEW OF ITS PHARMACODYNAMIC AND PHARMACOKINETIC PROPERTIES, AND THERAPEUTIC EFFICACY IN DEPRESSIVE-ILLNESS [J].
BENFIELD, P ;
WARD, A .
DRUGS, 1986, 32 (04) :313-334
[3]   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
[4]   FLUVOXAMINE-TRICYCLIC ANTIDEPRESSANT INTERACTION - AN ACCIDENTAL FINDING [J].
BERTSCHY, G ;
VANDEL, S ;
VANDEL, B ;
ALLERS, G ;
VOLMAT, R .
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 1991, 40 (01) :119-120
[5]   IMIPRAMINE DEMETHYLATION AND HYDROXYLATION - IMPACT OF THE SPARTEINE OXIDATION PHENOTYPE [J].
BROSEN, K ;
OTTON, SV ;
GRAM, LF .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1986, 40 (05) :543-549
[6]   ROLE OF P450IID6, THE TARGET OF THE SPARTEINE-DEBRISOQUIN OXIDATION POLYMORPHISM, IN THE METABOLISM OF IMIPRAMINE [J].
BROSEN, K ;
ZEUGIN, T ;
MEYER, UA .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1991, 49 (06) :609-617
[7]   THE EFFECT OF SELECTIVE SEROTONIN REUPTAKE INHIBITORS ON CYTOCHROME-P4502D6 (CYP2D6) ACTIVITY IN HUMAN LIVER-MICROSOMES [J].
CREWE, HK ;
LENNARD, MS ;
TUCKER, GT ;
WOODS, FR ;
HADDOCK, RE .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1992, 34 (03) :262-265
[8]  
GRAM LF, 1974, DAN MED BULL, V21, P218
[9]  
GRAM LF, 1975, CLIN PHARMACOL THER, V17, P555
[10]   THE P450 SUPERFAMILY - UPDATE ON NEW SEQUENCES, GENE-MAPPING, AND RECOMMENDED NOMENCLATURE [J].
NEBERT, DW ;
NELSON, DR ;
COON, MJ ;
ESTABROOK, RW ;
FEYEREISEN, R ;
FUJIIKURIYAMA, Y ;
GONZALEZ, FJ ;
GUENGERICH, FP ;
GUNSALUS, IC ;
JOHNSON, EF ;
LOPER, JC ;
SATO, R ;
WATERMAN, MR ;
WAXMAN, DJ .
DNA AND CELL BIOLOGY, 1991, 10 (01) :1-14