Pharmacokinetics and electrocardiographic effects of a new controlled-release form of flecainide acetate: comparison with the standard form and influence of the CYP2D6 polymorphism.

Objectives: Our objectives were study the single- and repeated-dose pharmacokinetics and electrocardiographic effects (QRS duration) of a new controlled-release form of flecainide acetate compared with the immediate-release form and to examine the influence of CYP2D6 activity.

Methods: Twenty-four healthy subjects (6 men and 6 women at both dosages) received single and repeated doses of 100 or 200 mg immediate-release and controlled-release flecainide in a randomized crossover design. Electrocardiograms were recorded and flecainide plasma concentrations were measured before administration and up to 96 hours after administration.

Particular cytochrome P-450-dependent steroid metabolism: a new class of mouse liver tumor markers.

An altered pattern of cytochrome P-450-dependent microsomal steroid metabolism was identified in female mouse liver tumors induced by 5,9-dimethyldibenzo[c,g]carbazole, a potent organo-specific liver carcinogen. These tumor tissues were compared to extratumoral liver parenchyme, to normal, fetal and neonatal livers and to spontaneous liver tumors, the frequency of which is very low in the highly hybridized mouse strain (XVIInc/Z) used for liver tumorigenesis. Cytochrome P-450-dependent steroid hydroxylase activities were measured by the identification and quantification of four monohydroxyprogesterone and eight monohydroxytestosterone metabolites.