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Titolo:
INHIBITION OF CYTOCHROME-P450 2D6 METABOLISM OF HYDROCODONE TO HYDROMORPHONE DOES NOT IMPORTANTLY AFFECT ABUSE LIABILITY
Autore:
KAPLAN HL; BUSTO UE; BAYLON GJ; CHEUNG SW; OTTON SV; SOMER G; SELLERS EM;
Indirizzi:
UNIV TORONTO,DEPT PHARMACOL,FAC MED,1 KINGS COLL CIRCLE TORONTO ON M5S 1A1 CANADA UNIV TORONTO,DEPT PHARMACOL,FAC MED TORONTO ON M5S 1A1 CANADA ADDICT RES FDN,BIOBEHAV RES DEPT TORONTO ON M5S 2S1 CANADA WOMENS COLL HOSP,PSYCHOPHARMACOL & DEPENDENCE RES UNIT TORONTO ON M5S1B2 CANADA UNIV TORONTO,FAC MED,DEPT MED & PSYCHIAT TORONTO ON CANADA UNIV TORONTO,FAC PHARM TORONTO ON CANADA
Titolo Testata:
The Journal of pharmacology and experimental therapeutics
fascicolo: 1, volume: 281, anno: 1997,
pagine: 103 - 108
SICI:
0022-3565(1997)281:1<103:IOC2MO>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
EXTENSIVE METABOLIZERS; POOR METABOLIZERS; DEBRISOQUINE; QUINIDINE; PHARMACOKINETICS; DEXTROMETHORPHAN; SPARTEINE; OXIDATION; PHENOTYPE; CODEINE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
27
Recensione:
Indirizzi per estratti:
Citazione:
H.L. Kaplan et al., "INHIBITION OF CYTOCHROME-P450 2D6 METABOLISM OF HYDROCODONE TO HYDROMORPHONE DOES NOT IMPORTANTLY AFFECT ABUSE LIABILITY", The Journal of pharmacology and experimental therapeutics, 281(1), 1997, pp. 103-108

Abstract

Enzymatic conversion of hydrocodone to hydromorphone is catalyzed by cytochrome P450 2D6, which is inactive in about 7% of Caucasians [poormetabolizers (PMs)] and can be inhibited by quinidine pretreatment inthe remainder [extensive metabolizers (EMs)]. If hydromorphone, having a substantially higher mu-receptor affinity than hydrocodone, contributes importantly to the physiological and subjective effects of oral hydrocodone, then PMs should be less responsive to the same doses, andquinidine pretreatment should cause EMs to temporarily respond as PMs. Seventeen EMs and 8 PMs who previously responded positively to hydromorphone s.c. received placebo and hydrocodone (10 mg, 15 mg and 22.5 mg p.o.) and were retested with their favorite dose after placebo or quinidine (100 mg) pretreatment; physiological and subjective measures were collected at base line and four times after drug administration, and urine was collected for 8 hr. EMs and PMs were equally responsive to oral hydrocodone, and quinidine had no consistent effect on their responses, even though quinidine abolished the pre-existing metabolic differences in hydromorphone production, as measured in urine. These data suggest only a small role of hydromorphone in eliciting abuse-related responses to oral hydrocodone.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/01/20 alle ore 12:48:30