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  • Title: Acecainide pharmacokinetics in normal subjects of known acetylator phenotype.
    Author: Coyle JD, Boudoulas H, Lima JJ.
    Journal: Biopharm Drug Dispos; 1991 Nov; 12(8):599-612. PubMed ID: 1724922.
    Abstract:
    The purpose of this study was to determine the pharmacokinetics of acecainide (formerly N-acetylprocainamide) in six normal subjects of known acetylator phenotype. Three subjects were fast acetylators and three slow acetylators by sulfapyridine phenotyping criteria. Each subject received a 20-min, 3 mg kg-1 intravenous acecainide infusion. Concentrations of acecainide, procainamide, and their deethylated metabolites were measured in serum and urine samples using HPLC. Acecainide renal clearance, nonrenal clearance, steady-state volume of distribution, and other pharmacokinetic parameters were estimated using standard approaches. Acecainide renal clearance and steady-state volume of distribution were (mean +/- SD) 13.6 +/- 1.581 h-1 and 135 +/- 20.31, respectively, and were not significantly different in fast and slow acetylators. Acecainide nonrenal clearance in the six subjects was 3.0 +/- 1.01 h-1; however, nonrenal clearance in slow acetylators was 1.8 times that in fast acetylators (3.9 vs 2.21 h-1, p = 0.012) with clear separation of the subjects into two groups when the data were grouped by acetylator phenotype. The nonrenal clearance of acecainide was inversely correlated with percentage sulfapyridine acetylation. Computer simulations were conducted to explore possible explanations for the observed difference in nonrenal clearance.
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