Pharmacokinetics of verapamil and norverapamil in patients with hypertension: a comparison of oral conventional and sustained release formulations.
A double blind, double dummy, randomized cross-over pharmacokinetic study comparing verapamil 120 mg, conventional tablets administered twice daily and verapamil 240 mg sustained release tablets once daily was performed in 12 patients with essential hypertension. After frequent blood sampling, analyses of verapamil and norverapamil were made with high pressure liquid chromatography. The absorption rate of the sustained release formulation was significantly slower than for the conventional formulation. Also the mean residence time was significantly longer for the sustained release tablet. It can be concluded that verapamil sustained release tablets meet with the following requirements for these formulations: (1) a slower absorption with an acceptable bioavailability relative to conventional tablets (89%); (2) no initial high peak concentration; (3) little fluctuation in the plasma concentration compared to the conventional formulation; (4) no differences in the elimination half lives for the two formulations; (5) maintenance of a therapeutic plasma level for a longer period of time than for the conventional formulation; (6) no increase in unwanted side effects.
Jørgensen
N P
NP
Clinical Department, Nycomed AS, Oslo, Norway.
Walstad
R A
RA
D000284:Administration, Oral; D001682:Biological Availability; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D011897:Random Allocation; D014700:Verapamil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*
D003692:Delayed-Action Preparations; C016904:norverapamil; D014700:Verapamil