Bioavailability of diltiazem as a function of the administered dose

Biopharm Drug Dispos. 1991 Jul;12(5):391-401. doi: 10.1002/bdd.2510120508.


Diltiazem undergoes extensive first-pass metabolism; extrapolation from single to repeated administration thus underestimates plasma concentration values. In order to validate the hypothesis of a partially saturable first-pass effect, four single doses of diltiazem (10, 20, 40, and 120 mg) were administered at weekly intervals to eight healthy volunteers. Results showed that: (a) the inter-subject variability was highest at the lowest dose at the highest dose; (b) bioavailability was almost nil in 3 of 8 of the subjects after the administration of the 10 mg dose; (c) the mean bioavailability increased with the dose from 11.8 +/- 2.5 per cent after 10 mg to 28.2 per cent after 120 mg; (d) the elimination half-life was dose-related; (e) the renal excretion of diltiazem increased with the administered dose from 1.0 +/- 0.3 per cent after 10 mg to 3.0 +/- 0.5 per cent after 120 mg; (f) the greatest amounts of circulating metabolites were present after the lowest doses. These results are consistent with a partially saturable first-pass effect for diltiazem.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Biological Availability
  • Chromatography, High Pressure Liquid
  • Diltiazem / administration & dosage
  • Diltiazem / pharmacokinetics*
  • Dose-Response Relationship, Drug
  • Humans
  • Male


  • Diltiazem