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Titolo:
THE CYP2D6 GENOTYPE AND PLASMA-CONCENTRATIONS OF MIANSERIN ENANTIOMERS IN RELATION TO THERAPEUTIC RESPONSE TO MIANSERIN IN DEPRESSED JAPANESE PATIENTS
Autore:
MIHARA K; OTANI K; TYBRING G; DAHL ML; BERTILSSON L; KANEKO S;
Indirizzi:
HIROSAKI UNIV HOSP,DEPT NEUROPSYCHIAT HIROSAKI AOMORI 036 JAPAN 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:
Journal of clinical psychopharmacology
fascicolo: 6, volume: 17, anno: 1997,
pagine: 467 - 471
SICI:
0271-0749(1997)17:6<467:TCGAPO>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
DEBRISOQUINE HYDROXYLATION; POOR METABOLIZERS; GENETIC-ANALYSIS; DESMETHYLMIANSERIN; LOCUS; AMPLIFICATION; POLYMORPHISM; BLOCKADE; CAPACITY;
Tipo documento:
Article
Natura:
Periodico
Citazioni:
25
Recensione:
Indirizzi per estratti:
Citazione:
K. Mihara et al., "THE CYP2D6 GENOTYPE AND PLASMA-CONCENTRATIONS OF MIANSERIN ENANTIOMERS IN RELATION TO THERAPEUTIC RESPONSE TO MIANSERIN IN DEPRESSED JAPANESE PATIENTS", Journal of clinical psychopharmacology, 17(6), 1997, pp. 467-471

Abstract

The relationship between therapeutic response to racemic mianserin and steady-state plasma concentrations of S(+)- and R(-)- mianserin was studied in 26 Japanese patients with major depression. The daily dose of mianserin was 30 mg, and the duration of treatment was 3 weeks. Regarding S-mianserin, the proportion of responders (final Montgomery-Asberg Depression Rating Scale score of 10 or less) was significantly higher in the plasma concentration range of 10 to 23 ng/mL than outside (10 of 11 vs. 3 of 15, p = 0.0005). Such a plasma concentration difference between responders and nonresponders was not found for R-mianserin. In 15 patients, the relationships between the CYP2D6 genotype, determined by allele-specific polymerase chain reaction analysis and Escherichia coli RI restriction fragment length polymorphism, plasma concentrations of the enantiomers, and the therapeutic response were studied. Five patients were homozygous for the wild type (wt) allele (wt/wt), nine were heterozygous for the CYP2DGCh (Ch) allele causing decreased CYP2D6 activity (Ch/wt), and one patient was heterozygous for the Ch allele and the defect allele CYP2DGD (D) (Ch/D). The Ch/wt group showedsignificantly higher plasma concentrations of S-mianserin (mean +/- SD: 15 +/- 6 vs. 8 +/- 1 ng/mL, p = 0.007) and proportion of responders(8 of 9 vs. 1 of 5, p = 0.023) than the wt/wt group. The patient withthe Ch/D genotype had the highest plasma concentration of S-mianserin(37 ng/ mL) and a poor response. No significant relationship was found between the CYP2D6 genotype and plasma concentration of S-mianserin. The study presented here thus suggests that the CYP2D6 genotype playsa major role in controlling plasma concentration of the S-enantiomer of mianserin, which contributes to a major extent to the antidepressant effect during mianserin treatment.

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Documento generato il 25/01/20 alle ore 09:20:32