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Bioavailability of diltiazem as a function of the administered dose
Author(s) -
Bianchetti G.,
Regazzi M.,
Rondanelli R.,
Ascalone V.,
Morselli P. L.
Publication year - 1991
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2510120508
Subject(s) - diltiazem , bioavailability , pharmacokinetics , pharmacology , half life , medicine , oral administration , dose–response relationship , chemistry , calcium
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.