Baicalin reduces ciclosporin bioavailability by inducing intestinal p-glycoprotein in rats

To investigate the effects of multiple doses of baicalin (BG) on the pharmacokinetics of ciclosporin (CsA) in rats and the potential mechanisms.

Pharmacokinetic parameters of CsA were determined in male rats after administration of CsA (3 mg/kg, i.g. or i.v.) to rats in the presence and absence of BG (80 mg/kg, i.g. or i.v.) for 7 days. The livers and intestines of rats were isolated and the CYP3A and p-glycoprotein (P-gp) expression were analysed. The effect of BG on the intestinal absorptive behaviour of CsA was also investigated using in-vitro everted rat gut sac model.

Baicalin (80 mg/kg, i.v., 7 days) had no effect on the intravenously administered CsA. However, BG (80 mg/kg, i.g., 7 days) significantly decreased the C_max , AUC_0-t and AUC_0-∞ of orally administered CsA by 38, 26 and 25%, respectively (P < 0.01 or P < 0.05). Further study revealed that the expression of P-gp in intestine increased in oral multiple doses of BG-treated rats. The in-vitro everted rat gut sac model demonstrated BG (10 μm) significantly decreased the absorption of CsA (10 μm) in intestine (P < 0.05).

Multiple doses of BG decreased the oral bioavailability of CsA in rats significantly, which may be mainly attributable to inhibition of absorption of CsA in intestine and induction of P-gp. The interaction between BG and CsA may occur when BG and CsA were co-administered for long-term use. The dosage adjustment and blood concentration monitoring of CsA may be required in clinic.