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Titolo:
Cytochrome P450 2D6 genotype and methadone steady-state concentrations
Autore:
Eap, CB; Broly, F; Mino, A; Hammig, R; Deglon, JJ; Uehlinger, C; Meili, D; Chevalley, AF; Bertschy, G; Zullino, D; Kosel, M; Preisig, M; Baumann, P;
Indirizzi:
Hop Cery, Unite Biochim & Psychopahrmacol Clin, Dept Univ Psychiat Adulte,CH-1008 Prilly Lausanne, Switzerland Hop Cery Prilly Lausanne SwitzerlandCH-1008 rilly Lausanne, Switzerland Ctr Hosp Reg & Univ Lille, F-59037 Lille, France Ctr Hosp Reg & Univ Lille Lille France F-59037 le, F-59037 Lille, France Hop Univ Geneve, Dept Psychiat, Chene Bourg, Switzerland Hop Univ Geneve Chene Bourg Switzerland chiat, Chene Bourg, Switzerland Univ Psychiat Dienst Bern, Bern, Switzerland Univ Psychiat Dienst Bern Bern Switzerland enst Bern, Bern, Switzerland Fdn Phenix, Geneva, Switzerland Fdn Phenix Geneva SwitzerlandFdn Phenix, Geneva, Switzerland Ctr Psychosocial, Fribourg, Switzerland Ctr Psychosocial Fribourg Switzerland ychosocial, Fribourg, Switzerland ARUD Zurich, Poliklin methadongestutzte Behandlung, ZOKL 1, Zurich, Switzerland ARUD Zurich Zurich Switzerland Behandlung, ZOKL 1, Zurich, Switzerland
Titolo Testata:
JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
fascicolo: 2, volume: 21, anno: 2001,
pagine: 229 - 234
SICI:
0271-0749(200104)21:2<229:CP2GAM>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
RESISTANT DEPRESSIVE PATIENT; HUMAN LIVER-MICROSOMES; CYP2D6 GENE; MAINTENANCE TREATMENT; INTERINDIVIDUAL VARIABILITY; ULTRARAPID METABOLISM; POOR METABOLIZERS; N-DEMETHYLATION; DEBRISOQUINE; POPULATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Eap, CB Hop Cery, Unite Biochim & Psychopahrmacol Clin, Dept Univ PsychiatAdulte,CH-1008 Prilly Lausanne, Switzerland Hop Cery Prilly Lausanne Switzerland CH-1008 usanne, Switzerland
Citazione:
C.B. Eap et al., "Cytochrome P450 2D6 genotype and methadone steady-state concentrations", J CL PSYCH, 21(2), 2001, pp. 229-234

Abstract

A genetic polymorphism of cytochrome P450 2D6 has been described with the existence of poor (zero functional genes), extensive (one or two functionalgenes), and ultrarapid metabolizers (three or more functional genes). The authors measured the steady-state trough (R)- (i.e., the active enantiomer), (S)-, and (R,S)-methadone plasma levels in opiate-dependent patients receiving methadone maintenance treatment (MMT) and genotyped them for cytochrome P4502D6. The patients' medical records were reviewed to assess the outcome of the MMT with regard to the absence of illicit opiate consumption and to the absence of withdrawal complaints in ultrarapid and poor metabolizers. Of 256 patients included, 18 were found to be poor metabolizers, 228 to be extensive metabolizers, and 10 to be ultrarapid metabolizers. Significantdifferences were found between genotypes for (R)- (p = 0.024), (S)- (p = 0.033), and (R,S)-methadone (p = 0.026) concentrations to dose-to-weight ratios. For (R)-methadone, a significant difference was found between ultrarapid metabolizers and poor metabolizers (p = 0.009), with the median value inthe former group being only 54% of the median value in the latter group. These results confirm the involvement of cytochrome P450 2D6 in methadone metabolism. Although the difference was nonsignificant (p = 0.103), 13 (72%) of the 18 poor metabolizers and only 4 (40%) of the 10 ultrarapid metabolizers were considered successful in their treatment. More studies are needed to examine the influence of the ultrarapid metabolizer status on the outcome of the MMT.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/01/20 alle ore 13:19:52