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Titolo:
Influence of hydroxychloroquine on the bioavailability of oral metoprolol
Autore:
Somer, M; Kallio, J; Pesonen, U; Pyykko, K; Huupponen, R; Scheinin, M;
Indirizzi:
Univ Turku, Dept Pharmacol & Clin Pharmacol, FIN-20520 Turku, Finland UnivTurku Turku Finland FIN-20520 n Pharmacol, FIN-20520 Turku, Finland
Titolo Testata:
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
fascicolo: 6, volume: 49, anno: 2000,
pagine: 549 - 554
SICI:
0306-5251(200006)49:6<549:IOHOTB>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
DEXTROMETHORPHAN METABOLISM; EUROPEAN POPULATION; CYP2D6 POLYMORPHISM; OXIDATION PHENOTYPE; HEALTHY-VOLUNTEERS; POOR METABOLIZERS; O-DEMETHYLATION; IN-VIVO; INHIBITION; DEBRISOQUINE;
Keywords:
CYP2D6; interaction; hydroxychloroquine (HCQ); metoprolol; dextromethorphan (DM);
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Kallio, J Univ Turku, Dept Pharmacol & Clin Pharmacol, Kiinamyllynkatu 10,FIN-20520Turku, Finland Univ Turku Kiinamyllynkatu 10 Turku Finland FIN-20520 , Finland
Citazione:
M. Somer et al., "Influence of hydroxychloroquine on the bioavailability of oral metoprolol", BR J CL PH, 49(6), 2000, pp. 549-554

Abstract

Aims Hydroxychloroquine (HCQ) is used widely in the treatment of chronic inflammatory diseases such as rheumatoid arthritis. Since there is great interindividual variability in the pharmacokinetics of HCQ and chloroquine is a potent inhibitor of CYP2D6-catalysed pathways in vitro, we wished to study the interaction of HCQ with CYP2D6-mediated metabolism of other drugs in vivo. Methods Metoprolol and dextromethorphan (DM) were selected as probe drugs because they are well-studied and widely used test substrates of CYP2D6. Inthis randomized, double-blind crossover study, seven healthy volunteers with extensive metabolizer phenotype for CYP2D6 ingested either 400 mg hydroxychloroquine or placebo daily for 8 days after which single oral dose pharmacokinetics of metoprolol were investigated. Dextromethorphan metabolic ratio (DM-MR) was also determined at baseline and after the ingestion of HCQ or placebo. Results Concomitant administration of HCQ increased the bioavailability ofmetoprolol, as indicated by significant increases in the area under the plasma concentration-time curve (65 +/- 4.6%) and maximal plasma concentrations (72 +/- 6.9%) of metoprolol. While the DM-MR values were not significantly changed, the phenotypic classification of one individual, who was heterozygous for a mutant CYP2D6 allele, was converted to a poor metabolizer by HCQ administration. Conclusions HCQ inhibits metoprolol metabolism most probably by inhibitingits biotransformation by CYP2D6. The inhibitory effect of HCQ on dextromethorphan metabolism was not apparent when DM-MR was used as an indicator, except in an individual with limited CYP2D6 capacity.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/01/20 alle ore 19:08:49