蟲草素及其代謝產物腺嘌呤在家兔之藥物動力學研究; Pharmacokinetics studies of Cordycepin and its Metabolite, Adenine in Rabbits

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題名:	蟲草素及其代謝產物腺嘌呤在家兔之藥物動力學研究;Pharmacokinetics studies of Cordycepin and its Metabolite, Adenine in Rabbits
作者:	劉美芳;Liu mei fang
貢獻者:	中國醫藥大學藥物化學研究所
關鍵詞:	蟲草素;腺嘌呤;Cordycepin;adenine
日期:	2004
上傳時間:	2010-01-20 16:55:48 (UTC+8)
摘要:	蟲草素(3'-脫氧腺?)是北蟲草分離之活性核?酸物質，可抑制核多聚腺?酸聚?，具有抗白血病、抗病毒及抗真菌作用。本研究針對蟲草素及其代謝產物腺嘌呤，進行在家兔之藥物動力學研究。利用自行開發的高效液相層析(HPLC)分析法定量血漿中蟲草素及腺嘌呤之濃度。層析條件包括使用Merck LiChrospher 100 RP-18e管柱，移動相為磷酸二氫鉀:甲醇 (92:8, pH7.0)，並以茶鹼為內部標準品，檢測波長為270 nm。蟲草素以兩種不同劑量(100、200 mg/kg)在家兔(N=6)進行靜脈注射之藥物動力學研究，發現蟲草素及其代謝產物腺嘌呤在家兔體內之經時變化，呈現一室模式。蟲草素靜脈輸注劑量100與200 mg/kg後其平均曲線下面積為154.515 ? 31.929和237.330 ? 42.602 ?g‧min/ml，平均半衰期為10.91 ? 2.45 和10.50 ? 3.58 min，擬似分布體積為10.237 ?1.731 和13.111 ? 5.059 L；其代謝產物腺嘌呤平均曲線下面積為1377.101 ? 580.752 和2844.352 ? 1012.145 ?g‧min/ml。腺嘌呤以二種不同劑量10與50 mg/kg在家兔(N=6)進行靜脈注射之藥物動力學研究，發現腺嘌呤的平均曲線下面積分別為120.921 ? 5.901 和1946.331 ? 601.503 ?g‧min/ml，平均半衰期為15.38 ? 1.65 和31.28 ? 7.57 min，擬似分布體積為2.038 ? 0.382 和1.166 ? 0.171 L。腺嘌呤以二種不同劑量50與100 mg/kg在家兔(N=6)進行口服給藥之藥物動力學研究，發現腺嘌呤的平均曲線下面積分別為1695.629 ? 258.846 和4138.236 ? 949.935 ?g‧min/ml，平均半衰期為41.38? 11.01 和55.01 ?12.89 min，擬似分布體積為1.783 ? 0.512 和1.936 ? 0.259 L。相關結果可以提供未來製劑學研究及一般使用者吸收方面資料等參考。; 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 ?g‧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 ?g‧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 ?g‧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 ?g‧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.
顯示於類別:	[藥物化學研究所] 博碩士論文

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