Influence of hydroxychloroquine on the bioavailability of oral metoprolol.

Article Details

Citation

Somer M, Kallio J, Pesonen U, Pyykko K, Huupponen R, Scheinin M

Influence of hydroxychloroquine on the bioavailability of oral metoprolol.

Br J Clin Pharmacol. 2000 Jun;49(6):549-54.

PubMed ID
10848718 [ View in PubMed
]
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. 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.

DrugBank Data that Cites this Article

Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
HydroxychloroquineCytochrome P450 2D6ProteinHumans
Unknown
Substrate
Inhibitor
Details