Different effect of erythromycin on absorption kinetics of nimodipine in male and female rats.

Effect of erythromycin (ERY) on oral absorption of nimodipine (NMD) in female and male rat was investigated in vivo and in vitro. In vivo, at 15 min following oral dose of 50 mg/kg ERY, an oral dose 20 mg/kg NMD was given to rats, plasma concentrations of NMD were determined. In vitro, everted jejunum sac and ileum sac were used, NMD transport from mucosal side to serol side was measured, in absences of ERY and cyclosprin A (CSA) or in presence of ERY and CSA. Large gender difference was found after oral dose NDM. Male rats had lower plasma concentration than female rat did. AUC180 and Cmax in male rats were less than 5-folds and 3-folds than those in female rats, respectively. Co-administrating ERY may increase plasma concentrations of NMD in rats. AUC180 in male rats and female rats were 2.2-folds and 1.9-folds of those NMD alone, respectively. Cmax was about 3-folds of that NMD alone. The NMD transport in intestine showed a regional variation and gender differences. In female rat, transport rate in the jejunum was about 1.3 higher than ileum. Both ERY and CSA significant increases transport of NMD. Contrast to female, NMD transport in jejunum was lower that that in ileum. Bothe ERY and CSA had little effect on NMD transport in intestine. These results indicated that there existed gender difference in oral absorption of NMD and effect of ERY on oral absorption kinetics of NMD in female rats was different from that in male rat.