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Biopharmaceutics & drug disposition

The influence of moderate and chronic exercise training on the pharmacokinetics of procainamide and N-acetylprocainamide.


PMID 9673780

Abstract

The effect of moderate and prolonged exercise on the disposition and metabolism of drugs has not been extensively examined. The present study examined the effect of exercise training on the pharmacokinetics of procainamide and its active metabolite, N-acetylprocainamide. Male Sprague Dawley rats were randomly assigned to three testing groups: (1) sedentary, (2) 4 weeks of exercise training and (3) 8 weeks of exercise training. Treadmill speed and exercise duration were gradually increased, reaching a final rate of 24 m min-1 for an hour by the end of the 4-week or 8-week period. Sedentary and exercise trained rats received a single i.p. dose of procainamide (100 mg kg-1). Serial blood samples were collected over a 10 h period and plasma samples were analysed by an UV-HPLC method. Noncompartmental analysis was performed to estimate the pharmacokinetic parameters. The t1/2 of procainamide was significantly (p < 0.05) higher in the 8 week exercise group (331 min) as compared to the sedentary group (77 min). In addition, there was a significant reduction in the amount of N-acetylprocainamide formed after 8 weeks of exercise (AUCNAPA = 739 ng mL-1 min-1). Results of this study suggest that prolonged exercise (8 weeks of training) alters the pharmacokinetics of procainamide by modifying the amount of active metabolite formed.

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