大白鼠併服枳實、枳殼對環孢靈動力學之影響   全文下載

Effects of Coadministrations of Unripe Fruits and Ripe Peels of Citrus aurantium on Cyclosporine Pharmacokinetics in Rats

枳實與枳殼分別為Citrus aurantium未成熟之果實及成熟之果皮，廣泛使用於中醫臨床。環孢靈為一治療指數極低之免疫抑制劑，臨床上發現葡萄柚汁與之發生交互作用。本研究以大白鼠為模型探討併服枳實、枳殼對環孢靈動力學之影響。以Sprague-Dawley大鼠口服投予環孢靈並分別併服枳實、枳殼水煎劑，心臟穿刺採血，利用螢光偏極免疫法定量血液中環孢靈濃度。結果顯示併服枳實對環孢靈血峰濃度與血藥面積分別顯著降低了72.8%與55.6%，而併服枳殼時則無影響。建議服用環孢靈之移植病患應避免併服柑橘屬中藥以確保療效與安全。

The unripe fruits (UF) and ripe peels (RP) of Citrus aurantium are two widely used Chinese herbs. Cyclosporine, an important immunosuppressant with narrow therapeutic window, is clinically subject to relevant interaction with Citrus herbs as with grapefruit juice. This study investigated the effects of coadministration of UF and RP on cyclosporine pharmacokinetics in rats. Sprague-Dawley rats received cyclosporine (2.5 mg/kg) orally with and without the UF and RP decoctions individually. Blood samples taken via cardiopuncture were assayed for cyclosporine by a specific monoclonal fluorescence polarization immunoassay. After coadministration orally with UF decoction, the Cmax and AUC0-t of cyclosporine were significantly decreased by 72.8% and 55.6%, respectively. However, when RP was coadministered orally, no conspicuous alteration of cyclosporine pharmacokinetics was observed. It can be concluded that UF, but not RP decoction, significantly decreased the bioavailability of oral cyclosporine. We suggest that coadministration of Citrus herbs with cyclosporine is better avoided to ensure the efficacy and safety of cyclosporin medication.