Pharmacokinetics of slow-release diltiazem and its effect on atrioventricular conduction in healthy volunteers.
The pharmacokinetics and effect of a slow-release and a conventional diltiazem tablet on atrioventricular conduction were compared in a randomized cross-over study after a single dose and at steady state in 12 healthy volunteers. The time to peak concentration was significantly delayed after the slow-release as compared to the conventional tablet, both after a single dose (2.7 vs. 0.9 h) and at steady-state (1.9 vs. 0.9 h). The peak concentration was also significantly reduced. There was no marked loss in bioavailability with the slow-release formulation. The maximal fluctuations in serum diltiazem at steady-state for the slow-release tablet were markedly less than after the conventional tablet (62 vs 87%). The PQ-interval was longer after the conventional tablet as compared to the slow-release tablet (both in doses of 120 mg) after a single dose (187 vs 163 ms) and at steady-state (197 vs 174 ms). The maximal prolongation was seen 1 h after intake of the drug. Heart rate was decreased only by 6-9 beats/min, irrespective of the dose. Slow-release diltiazem appears to have many advantages over a conventional tablet.
D000328:Adult; D003692:Delayed-Action Preparations; D004110:Diltiazem / Q000008:administration & dosage / Q000097:blood*; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008297:Male
D003692:Delayed-Action Preparations; D004110:Diltiazem