RELATIVE BIOAVAILABILITY OF 2 DISOPYRAMIDE CAPSULES IN HUMANS BASED ON TOTAL, UNBOUND, AND UNBOUND ENANTIOMER CONCENTRATIONS

The relative bioavailability of two 100-mg disopyramide formulations w hich showed almost an 8- to 10-fold difference in their dissolution ra tes at pH 1 . 2 and 6 . 8 was determined in eight healthy subjects usi ng a randomized block design. Although no significant differences in r elative bioavailability were observed between the two formulations whe n based on the total disopyramide concentration, an almost 30 per cent difference in the extent of bioavailability was observed when assesse d in terms of the unbound (+/-)- and (-)-disopyramide concentration, d ue 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 facto r for precise evaluation of the relative bioavailability of racemic dr ugs.