Circadian variation in the pharmacokinetics of verapamil

Summary Circadian variation in the metabolism of verapamil was investigated in 10 patients with stable angina pectoris during treatment with sustained-release verapamil 360 mg at 08.00 h or 22.0 h.No major difference in exercise parameters was found. During the evening dosage schedule a significantly greater bioavailability (AUC) and a prolonged time to peak concentration was found. During the night (24.00 h–06.00 h) the half-life of verapamil was significantly longer than during the day (16.00 h–22.00 h).These differences in pharmacokinetics may be due to reduced hepatic blood flow at night or to circadian variation in hepatic microsomal metabolism.