Pharmacokinetics of (+/-)-, (+)-, and (-)-gossypol in humans and dogs.

Pharmacokinetic parameters of (+/-)-, (+)-, and (-)-gossypol were determined in humans and dogs after a single oral or intravenous dose. Mean (+/- SD) oral bioavailability of (+/-)-gossypol in dogs was 30.9% +/- 16.2%. Studies in dogs who received single intravenous injections revealed that the elimination t1/2 and volume of distribution of (+)-gossypol were five and six times those of (-)-gossypol, respectively, whereas total body clearance and the AUC of the two enantiomers were similar. Data from men receiving the compounds orally show that the average peak plasma concentration and the AUC of (+)-gossypol are significantly greater than those of the (-)-isomer. The rate constants of alpha, beta, ka, k21, and k10 for (-)-gossypol are significantly greater than those for (+)-gossypol, indicating higher rates of mass transfer of the (-)-species. In humans the elimination t1/2 of (+)-gossypol was 29 times as that of (-)-gossypol, a difference that is more striking than that found in dogs. The elimination t1/2 of (+/-)-gossypol in humans averages 286 +/- 179 hours.