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Relative bioavailability of two disopyramide capsules in humans based on total, unbound, and unbound enantiomer concentrations
Author(s) -
Takahashi Harumi,
Ogata Hiroyasu,
Shimizu Mikiko,
Hashimoto Kayoko,
Masuhara Keiso,
Kashiwada Kazuko,
Someya Kazuhiko
Publication year - 1993
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.2510140507
Subject(s) - bioavailability , disopyramide , chemistry , enantiomer , chromatography , pharmacology , plasma concentration , pharmacokinetics , stereochemistry , medicine
The relative bioavailability of two 100‐mg disopyramide formulations which showed almost an 8‐ to 10‐fold difference in their dissolution rates at pH 1.2 and 6.8 was determined in eight healthy subjects using a randomized block design. Although no significant differences in relative bioavailability were observed between the two formulations when based on the total disopyramide concentration, an almost 30 per cent difference in the extent of bioavailability was observed when assessed in terms of the unbound (±)‐ and (−)‐disopyramide concentration, due probably to stereoselective nonlinear plasma protein binding. This suggests that unbound enantiomer parameters would be more sensitive to differences in bioavailability between two disopyramide formulations. Therefore, the type of concentration used would be an important factor for precise evaluation of the relative bioavailability of racemic drugs.