斯陆勤¹ 孙明辉² 何雪心¹ 张薇¹ 曹姗¹

（¹华中科技大学同济医学院药学院，武汉 430030

²同济医学院附属同济医院药学部，武汉 430030）

摘要：目的：研究环孢素A的全血浓度测定方法；以市售新山地明(Neoral^Ò)为参比制剂，评价自制环孢素A固体分散体(CsA-SD)在大鼠体内的药动学和相对生物利用度。方法：两组SD雄性大鼠分别单剂量给予CsA-SD和Neoral^Ò，按设计采集48h内动态血标本，采用HPLC法测定血药浓度。应用3P87药动学程序对数据进行拟合计算药动学参数。结果：单次给药后Neoral^Ò和CsA-SD的主要药动学参数C_max分别为(4029.7±405.8)ng ml^-1和(3958±1455)ng ml^-1，t_max分别为(1.54±0.57)h和(1.90±0.51)h，AUC_0→48分别为 (75072±25453)ng h ml^-1和(84861±26392)ng h ml^-1。统计分析结果显示，各主要药动学参数均无显著性差异。以Neoral^Ò为参比制剂，单剂量给药时CsA-SD的相对生物利用度为113.04%。结论：环孢素A固体分散体在大鼠体内显示与市售新山地明相近的生物利用度。

关键词  环孢素A 高效液相色谱法 生物利用度

Pharmacokinetics and relative bioavailability of cyclosporine A solid diepersion in rats

SI Luqin¹,SUN Minghui²,HE Xuexin¹, ZHANG Wei¹,CAO Shan¹,

(¹School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology;²Department of Pharmacy, Tongji Hospital Affiliated to the Tongji Medical College, Wuhan 430030,P.R.China)

ABSTRACT: OBJECTIVE：To study the pharmacokinetics and relative bioavailability of Cyclosporine A in rats. METHODS：The whole blood concentration of Cyclosporine A was determined by HPLC. Single dose po CsA-SD and Neoral^Ò were given to two groups of rats respectively. The data was processed with the software 3P87.The parameters were estimated with a statistic analysis of ANOVA. RESULTS：The C_max,,t_max,AUC_0→48 of Neoral^Ò and CsA-SD were (4029.7±405.8)ng ml^-1 and (3958±1455)ng ml^-1, (1.54±0.57)h and (1.90±0.51)h, (75072±25453) ng h ml^-1 and (84861±26392)ng h ml^-1, respectively.The mean relative bioavailability of the CsA-SD vs Neoral^Ò was 113.04%.The results of single oral administration 25mg/kg CsA demonstrated that two formulations were not bioequivalent.CONCLUSIONS： The results suggested that the Cyclosporine A solid dispersion has the similar bioavailability to Neoral^Ò.

KEY WORDS   cyclosporine A   HPLC   bioavailability