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Titolo:
CYP2D6 GENOTYPE AND PHENOTYPING BY DETERMINATION OF DEXTROMETHORPHAN AND METABOLITES IN SERUM OF HEALTHY CONTROLS AND OF PATIENTS UNDER PSYCHOTROPIC MEDICATION
Autore:
KOHLER D; HARTTER S; FUCHS K; SIEGHART W; HIEMKE C;
Indirizzi:
UNIV MAINZ,DEPT PSYCHIAT,UNTERE ZAHLBACHER STR 8 D-55101 MAINZ GERMANY UNIV VIENNA,DEPT PSYCHIAT,SECT BIOCHEM PSYCHIAT A-1090 VIENNA AUSTRIA
Titolo Testata:
Pharmacogenetics
fascicolo: 6, volume: 7, anno: 1997,
pagine: 453 - 461
SICI:
0960-314X(1997)7:6<453:CGAPBD>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
POLYMORPHIC DRUG OXIDATION; CYTOCHROMES P450; N-DEMETHYLATION; CYP3A ACTIVITY; IN-VIVO; POOR; 2D6; DEBRISOQUINE; HUMANS; ALLELE;
Keywords:
CYP2D6; DEXTROMETHORPHAN; DEXTRORPHAN; HYDROXYMORPHINAN; PHENOTYPING;
Tipo documento:
Article
Natura:
Periodico
Citazioni:
39
Recensione:
Indirizzi per estratti:
Citazione:
D. Kohler et al., "CYP2D6 GENOTYPE AND PHENOTYPING BY DETERMINATION OF DEXTROMETHORPHAN AND METABOLITES IN SERUM OF HEALTHY CONTROLS AND OF PATIENTS UNDER PSYCHOTROPIC MEDICATION", Pharmacogenetics, 7(6), 1997, pp. 453-461

Abstract

Fourteen drug free healthy volunteers and 22 psychiatric patients under psychotropic medication were phenotyped for their individual CYP2D6activity using dextromethorphan as a probe drug. A solution containing 20 mg dextromethorphan was administered and blood was taken 60 min later for determination of dextromethorphan and metabolites in serum. For comparison, urine was collected over 8 h after ingestion of 20 mg dextromethorphan in a separate test. The CYP2D6 phenotype was determined from the ratio of dextromethorphan to dextrorphan. For genotyping, mutant alleles of the CYP2D6 gene were identified using allele-specificpolymerase chain reactions. Genotyping revealed five poor metabolizers of CYP2D6. The others were extensive metabolizers. The ratio of dextromethorphan to dextrorphan ranged from 0.01-2.53 in serum and from 0.0007-4.252 in urine. Probit analysis of serum ratios revealed a bimodal distribution with an antimode at 0.126. According to this antimode, control subjects exhibited identical phenotypes and genotypes, whereaspatients under paroxetine, moclobemide or metoprolol who had been genotyped as extensive metabolizers were poor metabolizer phenotypes. Administration of tricyclic antidepressants did not change the CYP2D6 phenotype. The serum assay was more rapid and more accurate than the standard urine approach. Therefore the determination of dextromethorphan and metabolites in serum could be advantageous to measure individual CYP2D6 activities in vivo and thus optimize the dosing of drugs metabolized by CYP2D6.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/01/20 alle ore 10:57:14