Serum flecainide S/R ratio reflects the CYP2D6 genotype and changes in CYP2D6 activity.

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Doki K, Sekiguchi Y, Kuga K, Aonuma K, Homma M

Serum flecainide S/R ratio reflects the CYP2D6 genotype and changes in CYP2D6 activity.

Drug Metab Pharmacokinet. 2015 Aug;30(4):257-62. doi: 10.1016/j.dmpk.2015.04.001. Epub 2015 Apr 11.

PubMed ID

26195225 [ View in PubMed

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Abstract

The aims of this study were to clarify whether the ratio of S- to R-flecainide (S/R ratio) in the serum flecainide concentration was associated with the stereoselectivity of flecainide metabolism, and to investigate the effects of the cytochrome P450 (CYP) 2D6 (CYP2D6) genotype and CYP2D6 inhibitor on the serum flecainide S/R ratio. In vitro studies using human liver microsomes and cDNA-expressed CYP isoforms suggested that variability in the serum flecainide S/R ratio was associated with the stereoselectivity of CYP2D6-mediated flecainide metabolism. We examined the serum flecainide S/R ratio in 143 patients with supraventricular tachyarrhythmia. The S/R ratio was significantly lower in intermediate metabolizers and poor metabolizers (IMs/PMs) than in extensive metabolizers (EMs) identified by the CYP2D6 genotype. The cut-off value for the S/R ratio to allow the discrimination between CYP2D6 EMs and IMs/PMs was 0.99. The S/R ratio in patients with co-administration of bepridil, a potent CYP2D6 inhibitor, was lower than 0.99, regardless of the CYP2D6 genotype status. Other factors, including age, sex, body weight, and renal function, did not affect the serum flecainide S/R ratio. This study suggests that the serum flecainide S/R ratio reflects the CYP2D6 genotype and changes in CYP2D6 activity on co-administration of a CYP2D6 inhibitor.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Bepridil	Cytochrome P450 2D6	Protein	Humans	Unknown	Substrate Inhibitor	Details