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

Abstract

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.

Gender difference regarding schizandrin pharmacokinetics in rats

“…The absolute bioavailability in male rats was amounted to 17-fold less than that in female rats. This findings has also been reported for other drugs (12)(13)(14). The significant difference in absolute bioavailability between male and female rats indicates that this effect may have occurred before SZ reached the system circulation, and the observed difference in halflife (T1120) suggests that the difference in metabolism may one of the underlying factors.…”

Everted gut sac model as a tool in pharmaceutical research: limitations and applications

“…Due to physiological differences, different sex as well as species will influence drug pharmacokinetics. In female rat, transport rate of nimodipine in the jejunum was higher than ileum; and in contrast, nimodipine transport in male rat jejunum was lower than ileum [47] . In an everted gut sac study the transport, enzyme degradation and apparent permeation of leuprolide varied in different animal species (rabbits and rats).…”

“…animal factors (age, sex, species, diet, disease state, chronic treatment and toxicity), intestinal segment used (ileum, jejunum, duodenum and colon), and experimental factors (e.g. pH, aeration, temperature, concentration of substance); for other factors see Table 1) [45–69] .…”

Let’s talk about sex: Differences in drug therapy in males and females

“…In pre-clinical rat models Drug Sex differences in pharmacokinetic effect References Celastrol Higher oral bioavailability in female rats due to altered mechanism in absorption and metabolism [160] Clindamycin Higher plasma levels in female rats due to sex differences in CYP3A4, CYP2C9, CYP2C19 expression [161] Diltiazem Higher C max and longer t max in female rats than males [162] Letrozole Higher C max and AUC 0-480 in female rats; AUC and t 1/2 in females were 3-fold and 4-fold higher than in males Tissue/plasma drug concentration in female rats 24 h after dosing was significantly higher in female rats than in males in the heart, spleen, brain and genital glands [163] Letrozole Letrozole metabolism more extensive in male rats [163] Nimodipine Higher AUC 0-480 and C max in female rats [164] Ranolazine Significantly higher plasma concentrations in female rats than male rats; C max and AUC in female rats were roughly 2-to 3-fold greater [165] Ranolazine t 1/2 in male rats were shorter than in female rats [165] Schizandrin Higher C max and AUC 0-480 in female rats [166] Taurocholate Lower renal clearance in males [167]…”