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Titolo:
Effects of blocking CYP2D6 on the pharmacokinetics and pharmacodynamics ofoxycodone
Autore:
Heiskanen, T; Olkkola, KT; Kalso, E;
Indirizzi:
Univsinki,nki, Cent Hosp, Dept Anaesthesia, Pain Relief Unit, FIN-00029 Hel Univ Helsinki Helsinki Finland FIN-00029 Pain Relief Unit, FIN-00029 Hel
Titolo Testata:
CLINICAL PHARMACOLOGY & THERAPEUTICS
fascicolo: 6, volume: 64, anno: 1998,
pagine: 603 - 611
SICI:
0009-9236(199812)64:6<603:EOBCOT>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
CONTROLLED-RELEASE OXYCODONE; EXTENSIVE METABOLIZERS; HEALTHY-VOLUNTEERS; QUINIDINE TREATMENT; PSYCHOTROPIC-DRUGS; ABDOMINAL-SURGERY; POOR METABOLIZERS; MORPHINE; PAIN; CODEINE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Heiskanen, T Univ00029inki, Cent Hosp, Dept Anaesthesia, Pain Relief Unit,POB 260, FIN- Univ Helsinki POB 260 Helsinki Finland FIN-00029 B 260, FIN-
Citazione:
T. Heiskanen et al., "Effects of blocking CYP2D6 on the pharmacokinetics and pharmacodynamics ofoxycodone", CLIN PHARM, 64(6), 1998, pp. 603-611

Abstract

Background: Oxycodone is metabolized in the liver by means of O-demethylation to form oxymorphone in a reaction catalyzed by the enzyme cytochrome P450 2D6 (CYP2D6). This enzyme is expressed as 2 phenotypes (extensive and poor metabolizers), Several drugs are metabolized by CYP2D6, and clinically relevant drug interactions may occur. The aim of this study was to evaluate the role of oxymorphone in mediating the opioid effects of oxycodone by means of blocking CYP2D6 with quinidine,Methods: Ten healthy extensive metabolizers were administered 20 mg controlled-release oxycodone after premedication with placebo or 200 mg quinidinein this randomized, double-blind crossover study. A dose of 100 mg quinidine was administered 6 hours later. Plasma opioid concentrations, subjectivepharmacodynamic ratings, and psychomotor function were assessed for 24 hours after drug administration. Results: No oxymorphone was detected at any time after quinidine premedication in 8 of 10 subjects. Plasma oxycodone (difference not significant) andnoroxycodone (P<.01) concentrations were greater after quinidine pretreatment, Prevention of the production of oxymorphone by quinidine did not affect the psychomotor or subjective drug effects of oxycodone, No difference innumber of adverse effects was observed after the 2 pretreatments,Conclusions: A significant reduction in plasma oxymorphone levels did not substantially alter the pharmacodynamic effects of oxycodone, Analgesia wasnor evaluated because pain was not present.

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Documento generato il 26/01/20 alle ore 09:49:05