The effect of oral verapamil therapy on antipyrine clearance.

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.