The effect of oral verapamil therapy on antipyrine clearance.

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Abstract
The influence of chronic verapamil treatment on antipyrine elimination was studied in eight angina patients. Antipyrine half‐life (mean +/‐ s.d.) was 13.1 +/‐ 1.15 h at the start of therapy and 16.6 +/‐ 3.05 h (P less than 0.05) during chronic oral administration of verapamil (80‐ 120 mg four or three times daily for 4 to 7 months). There was a significant decrease in antipyrine clearance (mean +/‐ s.d, 43.2 +/‐ 16.8 ml min‐1 vs 28.7 +/‐ 16.6 ml min‐1, P less than 0.01) while the change of distribution volume was insignificant. Verapamil elimination was also found to be impaired after chronic dosing as compared to single administration. Half‐lives measured from the concentration vs time and urinary excretion rate vs time curves were both prolonged and oral clearance was decreased. Our results suggest that the inhibition of drug‐metabolizing enzymes accounts for the impairment of verapamil elimination on chronic administration.