Genetically determined stereoselective excretion of encainide in humans and electrophysiologic effects of its enantiomers in canine cardiac Purkinje fibers.
Clin Pharmacol Ther
; 49(5): 488-96, 1991 May.
Article
en En
| MEDLINE
| ID: mdl-1903098
ABSTRACT
Encainide metabolism is mediated by the polymorphically distributed cytochrome P450IID6, which displays stereoselectivity for some substrates. In this study we found that urinary recovery during steady-state encainide in three poor metabolizers was high (49% to 80%), consisted mainly of unchanged encainide, was nonstereoselective (+/- ratio, 0.985 to 1.049), and was unchanged by quinidine, a potent inhibitor of P450IID6. In contrast, in seven extensive metabolizers the +/- urinary ratios were 1.20 +/- 0.06 for encainide and 0.81 +/- 0.06 (both p less than 0.01) for the cytochrome P450IID6 products O-desmethylencainide plus 3-methoxy-O-desmethylencainide; with quinidine the total percentage recovery rose from 4% +/- 4% to 37% +/- 9% because of increased recovery of unchanged encainide and became non-stereoselective (+/- ratio, 0.84 +/- 0.08 [encainide alone] versus 0.97 +/- 0.05 [encainide plus quinidine]). In vitro, encainide enantiomers depressed the maximum rate of metabolism with similar frequency and concentration dependence. We conclude that (-)-encainide undergoes preferential metabolism by cytochrome P450IID6; however, this genetically determined stereoselective disposition is unlikely to play a major role in mediating the clinical actions of encainide.
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Bases de datos:
MEDLINE
Asunto principal:
Ramos Subendocárdicos
/
Anilidas
/
Antiarrítmicos
Idioma:
En
Revista:
Clin Pharmacol Ther
Año:
1991
Tipo del documento:
Article