Purpose: Cyclosporine is a widely used immunosuppressant with narrow therapeutic index and a substrate for CYP3A4 and P-glycoprotein (Pgp). Berberine is an alkaloid present in Chinese herbs likes Rhizoma Coptidis (RC) and Cortex Phellodendri (CP). Berberine was recently reported as a Pgp modulator. Therefore, our study attempted to investigate whether the coadministration of berberine, RC and CP would alter the absorption and disposition of cyclosporine. Methods: Rats were orally administered cyclosporine (2.5 mg/kg) with and without berberine (50 mg/kg) in parallel design. In addition, Rats were orally given cyclosporine with and without decoctions of RC ( 2 g/kg) or CP (2 g/kg) in crossover designs, respectively. Blood samples were withdrawn via cardiopuncture at specific time points post dosing. Blood cyclosporine concentrations were assayed by FPIA method. The pharmacokinetic parameters were calculated using WINNONLIN. Results: Berberine, CP and RC significantly decreased Cmax of cyclosporine by 88.2%, 58.5% and 50.6%, respectively, and AUC were significantly decreased by 86.3%, 55.0% and 40.0%, respectively. Conclusions: The coadministration of berberine, RC or CP markedly decreased the systemic exposure of cyclosporine. For the sake of safety, patients receiving cyclosporine treatment should avoid concurrent use of berberine or berberine –containing herbs
關聯:
2nd World congress of the board of Pharmaceutical sciences of FIP
