The Effect of Chinese Herbal Enhancer on Cyclosporin A Bioavailability

• Main Authors: Chin-hsing Yeh, 葉津杏
• Other Authors: none
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/12825118034418836720

碩士 === 嘉南藥理科技大學 === 生物科技系暨研究所 === 92 === Physiologically, P-glycoprotein is widely expressed in the epithelial cells of tissue, especially in the intestine, which is one of critical factors in drug absorption and disposition. Cyclosporin A is an immunosuppressant that used to prevent allograft rejection in transplantation. Since it is a substrate of CYP3A4 and P-glycoprotein, the absorption of cyclosporin A is highly variable and with a poor bioavailibity. As a result, the use of P-glycoprotein and CYP3A4 inhibitors may properly increase the absorption of cyclosporin A and may decrease the dose needed as well as blood concentration fluctuation in cyclosporin A treatment. HUCHE is a compound of Chinese herbal enhancer. It is monoterpene found in the essential oil of several useful plants. It has been reported HUCHE may inhibit Cytochrome 450 and P-glycoprotein activity. In this study, the rats were treated with different cyclosporin A formulations with and without HUCHE to explore the effect of Chinese herbal enhancer as well as formulation on cyclosporin A absorption. The blood cyclosporin A concentration was determined by fluorescence polarization immunoassay (FPIA). The results showed that organic-base solvent had better absorption than oil-base solvent. Different cyclosporin A (10 mg/kg) formulas coadministered HUCHE showed that HUCHE can increased NEORAL® and formula 1 (F1; alcohol, olive oil) oral absorption, and the area under the concentration-time curve from time zero to 24 hours (AUC0~24 ) increased 54% and 58% (p<0.05), respectively. The AUC0~24 of formula 3 (F3; alcohol, Tween 80, propylene glycol) with HUCHE compared with that of NEORAL® increased 2 folds. However, Cmax and AUC0~24 decreased in the olive oil formulation coadministered with HUCHE. The study suggests that through the inhibition of CYP3A4 and P-glycoprotein, HUCHE may improve the bioavailability of some cyclosporin A formulas.