Study on intestinal absorption characteristics of apixaban by in vivo one-way perfusion in rats with renal failure / 药学实践与服务

ABSTRACT

Objective To study the intestinal absorption characteristics of apixaban in rats with renal failure, and the effect of P-glycoprotein (P-gp) inhibitors on its absorption behavior. Methods The in vivo absorption experiment was performed in CRF rats by one-way perfusion method and the absorption factors was investigated by establishing the HPLC analysis method. Results The absorption rate constant (Ka) of apixaban in each intestinal segment was significantly different (P<0.05) with no significant difference in apparent absorption coefficient (Papp) (P>0.05). The Ka and Papp values in the rat ileum decreased with the increasing of drug concentration. After addition of P-gp inhibitor verapamil hydrochloride (0.1 mmol/L), the Ka and Papp values of apixaban in the jejunum and ileum were significantly increased. Conclusion Apixaban is absorbed in all intestinal segments. P-gp inhibitors can significantly promote the absorption of apixaban in jejunum and ileum, suggesting that apixaban is P-gp substrate and its absorption mechanism is supposed to be active transport.