Study of pharmacokinetics of digoxin in ovariectomized rats model

This study aims to investigate the change of plasma concentration of digoxin(DIG) in rats with ovariectomy. Twelve female SD rats were randomly assigned into ovariectomized group and sham group(n=6). All rats plasma was collected after a single dose of 2 mg·kg-1 DIG administrated orally, serum DIG concentration was determined by LC-MS/MS. The level of P-gp in the intestinal was analyzed by Western blotting. Pharmacokinetic calculations were performed on each individual using DAS 2.0 practical pharmacokinetic software. Compared with the sham group, C_max of ovariectomized group decreased significantly(P<0.01). There was no significant difference of AUC_0-t and the level of P-gp was elevated in ovariectomized group. It was found that C_max of DIG was significantly reduced after ovariectomy, and the change was associated with the decreased level of estrogen, which contributes to the increased level of P-gp.