冬蟲夏草顯著降低環孢靈於鼠體內之吸收   全文下載

Marked Decrease of Cyclosporin Absorption Caused by Coadministration of Cordyceps sinensis in Rats

冬蟲夏草在台灣及中國大陸為常用之補益藥，環孢靈於臨床上則為重要之免疫抑制劑，但其治療指數很小，因此本研究探討併服冬蟲夏草於鼠體內對環孢靈動力學之影響。本研究分別以靜脈注射（0.8 mg/kg）或口服（2.5 mg/kg）給予環孢靈，以交叉設計給藥，實驗組口服給予冬蟲夏草（2.0 g/kg），對照組則給予等體積蒸餾水，以心臟採血方式於特定時間點採取血液樣本。血液樣本以偏極螢光免疫分析方法（FPIA）分析環孢靈血中濃度，並以非室體模式計算口服及靜脈注射環孢靈之動力學參數，以paired Student’s t-test比較組間差異。結果發現同時服用冬蟲夏草時，口服環孢靈之Cmax與AUC0-540顯著降低了85.5%與83.2%；此外，於口服環孢靈前一小時先給予冬蟲夏草，其Cmax與AUC0-540亦顯著降低了85.9%與84.4%,；然而環孢靈以靜脈注射給予時，其動力學參數並不受到併服冬蟲夏草之影響，顯示二者之交互作用應發生於吸收過程。以上結果顯示併服冬蟲夏草顯著降低環孢靈之生可用率，因此使用環孢靈之病人應建議其避免同期使用冬蟲夏草，以確保藥效及安全性。"

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.