Bioavailability of diltiazem as a function of the administered dose

G. Bianchetti, M. Regazzi, R. Rondanelli, V. Ascalone, P. L. Morselli

Research output: Contribution to journalArticle

Abstract

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 and lowest 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.

Original languageEnglish
Pages (from-to)391-401
Number of pages11
JournalBiopharmaceutics and Drug Disposition
Volume12
Issue number5
Publication statusPublished - 1991

Keywords

  • Bioavailability
  • Diltiazem
  • First-pass
  • Healthy volunteers

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Fingerprint Dive into the research topics of 'Bioavailability of diltiazem as a function of the administered dose'. Together they form a unique fingerprint.

  • Cite this

    Bianchetti, G., Regazzi, M., Rondanelli, R., Ascalone, V., & Morselli, P. L. (1991). Bioavailability of diltiazem as a function of the administered dose. Biopharmaceutics and Drug Disposition, 12(5), 391-401.