Pharmacokinetic analysis of two new sustained-release products of diltiazem designed for twice- and once-daily treatment.
The pharmacokinetics of two new sustained-release (SR) products of diltiazem, Dilapress 120 mg tablets and Dilapress 240 mg tablets, was analysed and characterized in three different studies, in comparison to the following diltiazem SR formulations: Cardizem Retard, Cardizem SR, and Cardizem CD. Dilapress 120, designated for twice-daily dosing, was found to be bioequivalent to Cardizem SR and to Cardizem Retard with mean (+/- SD) relative bioavailability values of 99 +/- 27% and 113 +/- 38%, respectively. Dilapress 240, designed for once-a-day treatment, was found to have a slower absorption rate than Cardizem SR and its extent of absorption was 56 +/- 19% relative to that of Cardizem SR. However, the bioavailability of Dilapress 240 relative to that of Cardizem CD was 118 +/- 46%, indicating that the bioavailability of Cardizem CD relative to that of Cardizem SR was only 54 +/- 29%. Diltiazem is partially available due to a saturable liver first-pass effect. A high dose of Cardizem SR may partially escape this first-pass effect and, thus, achieve a higher extent of absorption than a slower SR product. Consequently, SR products of diltiazem designed for once-daily treatment may not reach the saturation stage in the liver first-pass effect process that diltiazem is susceptible to. Consequently, a twice-daily SR product of diltiazem cannot serve as a reference for extent of absorption assessments of a once-daily SR product.
Bialer
M
M
Department of Pharmacy, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Israel.
Hadad
S
S
Golomb
G
G
Barel
S
S
Samara
E
E
Abu Salach
O
O
Berkman
N
N
Danenberg
H D
HD
Ben David
J
J
Caron
D
D
D000042:Absorption; D000704:Analysis of Variance; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D004110:Diltiazem / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D006801:Humans
D003692:Delayed-Action Preparations; D004110:Diltiazem