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Titolo:
EFFECTS OF THIORIDAZINE, AN INHIBITOR OF CYP2D6, ON THE STEADY-STATE PLASMA-CONCENTRATIONS OF THE ENANTIOMERS OF MIANSERIN AND ITS ACTIVE METABOLITE, DESMETHYLMIANSERIN, IN DEPRESSED JAPANESE PATIENTS
Autore:
YASUI N; TYBRING G; OTANI K; MIHARA K; SUZUKI A; SVENSSON JO; KANEKO S;
Indirizzi:
HIROSAKI UNIV HOSP,DEPT NEUROPSYCHIAT HIROSAKI AOMORI 036 JAPAN HUDDINGE UNIV HOSP,KAROLINSKA INST,DEPT MED LAB SCI & TECHNOL,DIV CLIN PHARMACOL S-14186 HUDDINGE SWEDEN
Titolo Testata:
Pharmacogenetics
fascicolo: 5, volume: 7, anno: 1997,
pagine: 369 - 374
SICI:
0960-314X(1997)7:5<369:EOTAIO>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
POOR METABOLIZERS; DRUG OXIDATION; DEBRISOQUINE; ALLELE; LOCUS; GENE; HYDROXYLATION; AMPLIFICATION; POLYMORPHISM; DIAZEPAM;
Keywords:
MIANSERIN; DESMETHYLMIANSERIN; ENANTIOMERS; THIORIDAZINE; CYP2D6;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
21
Recensione:
Indirizzi per estratti:
Citazione:
N. Yasui et al., "EFFECTS OF THIORIDAZINE, AN INHIBITOR OF CYP2D6, ON THE STEADY-STATE PLASMA-CONCENTRATIONS OF THE ENANTIOMERS OF MIANSERIN AND ITS ACTIVE METABOLITE, DESMETHYLMIANSERIN, IN DEPRESSED JAPANESE PATIENTS", Pharmacogenetics, 7(5), 1997, pp. 369-374

Abstract

The antidepressant mianserin is administered as a racemate of the S(+)- and R(-)-enantiomers. Previous in-vitro studies have suggested thatCYP2D6 is involved in the stereoselective metabolism of mianserin andits active metabolite, desmethylmianserin. To determine a role for (CYP2D6 in vivo, the effects of thioridazine, an inhibitor of CYP2D6, onthe steady-state plasma concentrations of the enantiomers of mianserin and desmethylmianserin were examined in 13 depressed Japanese patients. All patients were taking 30 mg of racemic mianserin at bedtime for8-50 days. Thioridazine (40 mg/day) was coadministered for 1 week, and blood samplings were performed before and after thioridazine coadministration, 12 h after bedtime dosing, Plasma concentrations of the enantiomers of mianserin and desmethylmianserin were measured by HPLC, and the CYP2D6 genotype was determined by allele-specific PCR analysis. Thioridazine significantly increased plasma concentration of S(+)-mianserin (mean SD:78.2+/-35.0 vs, 150.8+/-48.7 nM, P<0.001), but not R(-)-mianserin (39.8+/-21.2 vs. 39.5+/-20.6 nM, NS). Thioridazine also significantly increased plasma concentrations of both S-desmethylmianserin (11.9+/-2.8 vs. 24.4+/-10.7 nhl, P<0.01) and R-desmethylmianserin (42.6+/-28.4 vs. 115.6+/-36.9 nM, P < 0.001). One patient homozygous forthe defective allele CYP2D65 had the second highest and highest plasma concentrations of S(+)-mianserin and R-desmethylmianserin, respectively, before thioridazine coadministration, and exhibited little increase in plasma concentration of the drugs after thioridazine coadministration. These results suggest that thioridazine specifically inhibits the metabolism of S(+)-mianserin and R-desmethylmianserin, probably through inhibition of CYP2D6, but not R(-)-mianserin.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 09:30:20