替米沙坦片人体药动学及生物等效性.doc

替米沙坦片人体药动学及生物等效性 　 作者：黄鹏，张红，徐文炜，李艳艳，熊玉卿 【关键词】 替米沙坦；色谱法,高压液相；生物等效性 　　Pharmacokinetics and bioequivalence of telmisartan in Chinese healthy volunteers 　　【Abstract】 AIM: To develop a HPLC method with fluorescent detection to determine telmisartan in human plasma and study the pharmacokinetics profiles and bioequivalence of telmisartan in healthy Chinese volunteers. METHODS: In a randomized two period crossover study, 24 healthy male volunteers received single dose of 40 mg telmisartan. The serum concentration of telmisartan was determined by HPLC method. The pharmacokinetic parameters of the two preparations (test and reference) and the relative bioavailability after oral administration were calculated with statistic analysis. The column was Diamonsil C18 (5 μm, 4.6 mm×150 mm). The mobile phase consisted of acetonitrilepotassium dihydrogen phosphate buffer solution (61∶39, pH adjusted to 3.74 with H3PO4) at a flow rate of 1.0 mL/min. The internal standard was candesartan. The fluorescence detector was operated at λEx=305 nm and λEm=365 nm. RESULTS: The calibration curve of telmisartan was linear in the range of 0.5-144 ng/mL (r=0.9998). The absolute recovery was 79.62%-85.69% (n=5), and the relative recovery was 101.92%-108.95% (n=5), and the intraday and interday RSDs were 4.23%-9.80% and 4.03%-9.95% (n=5). AUC0~96 of the test and reference preparations was 888.90±406.49 and 895.03±364.53, respectively. CONCLUSION: Statistical analysis showed that the two preparations were bioequivalent. 　　【Keywords】 telmisartan; chromatography, high pressure liquid; bioequivalent 　　【摘要】 目的： 建立测定替米沙坦血浆浓度的高效液相荧光检测法（HPLC），考察替米沙坦的药代动力学及生物等效性. 方法： 24例健康受试者单剂量交叉口服40 mg替米沙坦片供试制剂或参比制剂后，用HPLC测定替米沙坦血药浓度并计算药动学及相对生物利用度，进而对主要药动学参数进行统计分析. 色谱柱为Diamonsil C18柱（5 μm, 4.6 mm×150 mm），以乙腈磷酸二氢钾缓冲液（61∶39，磷酸调pH=3.74）为流动相，流速1.0 mL/min，坎地沙坦为内标，荧光检测波长λEx=305 nm, λEm=365 nm. 结果： 测定替米沙坦的线性范围为0.5～144 ng/mL, r=0.9998，绝对回收率在79.62%～85.69%（n=5），相对回收率在101.92%～108.95%（n=5），日内和日间RSD分别为4.23%～9.80%和4.03%～9.95%（n=5）. 供试制剂