Bioavailability of diltiazem as a function of the administered dose

✍ Scribed by G. Bianchetti; M. Regazzi; R. Rondanelli; V. Ascalone; P. L. Morselli

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: English
• Weight: 512 KB
• Volume: 12
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/bdd.2510120508

✦ Synopsis

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 f 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 f 0.3 per cent after 10 mg to 3.0 f 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.