Pharmacokinetics studies of Cordycepin and its Metabolite, Adenine in Rabbits

• Main Authors: Liu mei fang, 劉美芳
• Other Authors: Cheng-Hsiung Liu
• Format: Others
• Language: zh-TW
• Published: 2005
• Online Access: http://ndltd.ncl.edu.tw/handle/30991011160791223159

碩士 === 中國醫藥大學 === 藥物化學研究所 === 93 === Cordycepin (3'-deoxyadenosine) is a nucleoside derivative isolated from cultured fluids of Cordyceps militaris, shown to inhibit poly (A) tail-RNA polymerases. Cordycepin was discovered to have antileukemia, anti-HIV and antifungal activity. In this study, a simple and sensitive high-performance liquid chromatographic(HPLC) method was developed for the determination of cordycepin and its metabolite, adenine, in rabbit blood. A HPLC system equipment with a Merck LiChrospher 100 RP-18e column was used in the assay of cordycepin and adenine. Theophylline was chosen as the internal standard. The mobile phase consisted of potassium dihydrogenphosphate - methanol (92:8, pH7.0) and UV detection wavelength was at 270 nm. After iv bolus administration of the cordycepin at the doses of 100 and 200 mg/kg to the rabbits, the plasma level-time profiles of cordycepin and its metabolite, adenine,were adequately described by the one-compartment open model. The mean area under the serum concentration curve (AUC0-∞) were about 154.515  31.929 and 237.330  42.602 µg•min/ml, respectively. The mean half-life (T1/2) were about 10.91  2.45 and 10.50  3.58 min. The volumes of apparent distribution were 10.237 1.731 and 13.111  5.059 L. As well as its metabolite, adenine, the mean area under the serum concentration curve (AUC0-∞) were about 1377.101  580.752 and 2844.352  1012.145 µg•min/ml. The pharmacokinetics of adenine in the rabbits after iv bolus administration of two doses 10 and 50 mg/kg, the mean area under the serum concentration curve (AUC0-∞) were about 120.921  5.901 and 1946.331  601.503 µg•min/ml, respectively. The mean half-life (T1/2) were about 15.38  1.65 min and 31.28  7.57 min. The volumes of apparent distribution were 2.038  0.382 and 1.166  0.171 L. The pharmacokinetic study of 50 and 100 mg/kg of adenine were designed as oral administration to rabbits. The mean area under the serum concentration curve (AUC0-∞) were 1695.629  258.846 and 4138.236  949.935 µg•min/ml. The mean half-life (T1/2) were about 41.38 11.01 and 55.01 12.89 min. The volumes of apparent distribution were 1.783  0.512 and 1.936  0.259 L. These results may be useful in support of the dosage forms design and provide to general use information.