Pharmacokinetic analysis of two new sustained-release products of diltiazem designed for twice- and once-daily treatment

Biopharm Drug Dispos. 1994 Jan;15(1):45-52. doi: 10.1002/bdd.2510150104.


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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial

MeSH terms

  • Absorption
  • Analysis of Variance
  • Biological Availability
  • Chromatography, High Pressure Liquid
  • Delayed-Action Preparations
  • Diltiazem / administration & dosage
  • Diltiazem / blood
  • Diltiazem / pharmacokinetics*
  • Drug Administration Schedule
  • Humans


  • Delayed-Action Preparations
  • Diltiazem