Influence of hydroxychloroquine on the bioavailability of oral metoprolol

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...

Full description

Saved in:

Bibliographic Details
Published in:	British journal of clinical pharmacology Vol. 49; no. 6; pp. 549 - 554
Main Authors:	Somer, Mika, Kallio, Jaana, Pesonen, Ullamari, Pyykkö, Kaija, Huupponen, Risto, Scheinin, Mika
Format:	Journal Article
Language:	English
Published:	Oxford, UK Blackwell Science Ltd 01-06-2000 Blackwell Science Inc
Subjects:	Adrenergic beta-Antagonists - pharmacokinetics Adult Antimalarials - pharmacology Antirheumatic Agents - pharmacology Area Under Curve Biological Availability Chromatography, High Pressure Liquid Cross-Over Studies CYP2D6 Cytochrome P-450 CYP2D6 Inhibitors dextromethorphan (DM) Dextromethorphan - urine Double-Blind Method Drug Interactions Half-Life Humans hydroxychloroquine (HCQ) Hydroxychloroquine - pharmacology interaction Male metoprolol Metoprolol - pharmacokinetics Pharmacogenetics
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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. In this 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 of metoprolol, 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 inhibiting its 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.
ISSN:	0306-5251 1365-2125
DOI:	10.1046/j.1365-2125.2000.00197.x