Relative bioavailability of two disopyramide capsules in humans based on total, unbound, and unbound enantiomer concentrations
✍ Scribed by Harumi Takahashi; Hiroyasu Ogata; Mikiko Shimizu; Kayoko Hashimoto; Keiso Masuhara; Kazuko Kashiwada; Kazuhiko Someya
- Publisher
- John Wiley and Sons
- Year
- 1993
- Tongue
- English
- Weight
- 514 KB
- Volume
- 14
- Category
- Article
- ISSN
- 0142-2782
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✦ Synopsis
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.