Effect of CYP2D6 genetic polymorphism on peak propafenone concentration: no significant effect of CYP2D6*10

Author:

Doki Kosuke1ORCID,Shirayama Yuki1,Sekiguchi Yukio2,Aonuma Kazutaka2,Kohda Yukinao1,Ieda Masaki2,Homma Masato1

Affiliation:

1. Department of Pharmaceutical Sciences, Faculty of Medicine, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki, 305 8575, Japan

2. Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki, 305 8575, Japan

Abstract

Aim: The study aims to investigate the clinical implication of nonfunctional poor metabolizer (PM) alleles and intermediate metabolizer (IM) alleles of CYP2D6, including the CYP2D6*10 allele which shows substrate-dependent decrease in enzymatic activity, in antiarrhythmic therapy using propafenone. Materials & methods: We examined serum propafenone concentrations and metabolic ratio, which was expressed as serum concentrations of propafenone to 5-hydroxypropafenone, in 66 Japanese patients with tachyarrhythmias. Results: The peak propafenone concentration and metabolic ratio in CYP2D6 PM allele carriers were higher than those in extensive metabolizer (EM)/EM, EM/IM and IM/IM genotype groups. Conclusion: Results suggest that CYP2D6 PM alleles affect peak propafenone concentration, but the CYP2D6 IM allele CYP2D6*10 has no clinical implication in propafenone dosing.

Funder

Japan Research Foundation for Clinical Pharmacology

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

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