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Article Title

Marked decrease of cyclosporin absorption caused by coadministration of Cordyceps sinensis in rats

Abstract

Cordyceps (Cordyceps sinensis Saccardo.) is a popular traditional tonic used in Taiwan and mainland China. Cyclosporin is an important immunosuppressant with narrow therapeutic index. This study investigated the effect of coadministration of cordyceps on cyclosporin pharmacokinetics in rats. Cyclosporin was intravenously (0.8 mg/kg) and orally (2.5 mg/kg) administered with and without cordyceps (2.0 g/kg), respectively, in crossover designs. Blood samples were collected by cardiopuncture and quantitated by a specific monoclonal fluorescence polarization immunoassay. Pharmacokinetic parameters of cyclosporin were calculated using noncompartment model. Paired Student's t-test was used for statistical comparison. Our results indicated that oral coadministration of cordyceps significantly decreased the Cmax and AUC0-540 of cyclosporin by 85.5% and 83.2%, respectively. In addition, when rats were given cordyceps 1 hr before cyclosporin dosing, the Cmax and AUC0-540 of cyclosporin were significantly decreased by 85.9% and 84.4%, respectively. By contrast, when cyclosporin was given as an intravenous bolus, the disposition of cyclosporin was not altered by cordyceps, indicating that the interaction between oral cyclosporin and cordyceps occurred during the absorption phase. In conclusion, cordyceps markedly decreased the oral bioavailability of cyclosporin. Patients treated with cyclosporin are suggested to avoid the concurrent use of cordyceps for efficacy and safety.

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