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The effect of verapamil on antipyrine pharmacokinetics and metabolism in man.

The effect of verapamil pre-treatment on the pharmacokinetics and metabolism of antipyrine was studied in eight healthy male volunteers. The oral clearance of antipyrine was decreased from 2.18 to 1.95 l h-1 (P less than 0.01) by verapamil (80 mg three times daily for 2 days prior to antipyrine administration and 2 days following) while half-life was increased from 13.2 to 15.6 h (P less than 0.01). The urinary excretion of norantipyrine, 4-hydroxyantipyrine and 3-hydroxymethylantipyrine was decreased by 19.2%, 23.1% and 16.7% respectively (P less than 0.05) in the presence of verapamil. In addition, the rate constants for formation of each of these metabolites were significantly decreased by an average of approximately 30%. These results suggest that verapamil is capable of inhibiting oxidative metabolism, a finding which could be of clinical significance for drugs highly dependent upon pathways such as those inhibited in this study for elimination.