Purpose: Soybeans are consumed in many Asian countries and provide a major source of isoflavones. Nowadays, western people turn to ingest soybean extract as dietary supplement. Many studies indicated that isoflavones modulate CYP3A4 and Pgp. Cyclosporin is a widely used immunosuppressant with narrow therapeutic index and a substrate for CYP3A4 and P-glycoprotein (Pgp). Our study attempted to investigate whether the coadministration of soybean would alter the absorption and disposition of cyclosporin. Methods: Rats were intravenously or orally administered cyclosporin with and without soybean extracts (8 g soybean/kg) in crossover designs. Blood samples were withdrawn via cardiopuncture at predetermined time points and cyclosporin blood concentrations were assayed by FPIA method. The pharmacokinetic parameters of cyclosporin were calculated by using WINNONLIN. Paired student’s t-test was used for statistical comparison. Results: The coadministration of soybean extracts significantly decreased Cmax and AUC of oral cyclosporin by 58% and 59%, respectively, whereas the pharmcokinetics of intravenous cyclosporin was not affected. It implies that the interaction occurred at the absorption site. Conclusions: Concurrent use of soybean extracts significantly decreased the bioavailability of oral cyclosporin. Patients treated with cyclosporin should be discouraged from using soybean products concomitantly.
關聯:
2nd World congress of the board of Pharmaceutical sciences of FIP
