Circadian variation in the pharmacokinetics of verapamil.
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.
Jespersen
C M
CM
Department of Cardiology, Hvidovre Hospital, Denmark.
Frederiksen
M
M
Hansen
J F
JF
Klitgaard
N A
NA
Sørum
C
C
D000787:Angina Pectoris / Q000188:drug therapy*; D001682:Biological Availability; D002940:Circadian Rhythm; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005080:Exercise Test; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D011897:Random Allocation; D014700:Verapamil / Q000097:blood / Q000493:pharmacokinetics*
D003692:Delayed-Action Preparations; D014700:Verapamil