国产左氧氟沙星片剂健康人体生物等效性研究

Bioequivalence study of Levofloxacin Tablets in Chinese Healthy Volunteers

目的：研究国产左氧氟沙星片剂（可乐必妥）的相对生物利用度并求证该制剂的生物等效性。方法：２１名男性健康受试者随机交叉给药，分别口服单剂量左氧氟沙星国产片剂（试验制剂）及进口片剂（参比制剂），采用反相高效液相色谱法测定血及尿药浓度，计算两者的药代动力学参数及相对生物利用度，并求证国产片与进口片的等效性。结果：口服左氧氟沙星２００ｍｇ国产及进口片剂的主要药代力学参数ｔ１／２６分别为６．１４±０．４６和６．２４±０．４８ｈ；ｔ０．９２±０．４０ｈ；Ｃｍａｘ分别为 ２，７６ ± ０．４７和 ２．６９ ± ０，４５ ｍｇ·Ｌ－１；ＡＵＣｏ－ｐ；分别为 １８．１５ ± ２．２３和 １８．０７±２．０１ ｍｇ·ｈ·Ｌ－１； ＡＵＣ０－９．３１± ２．２８和 １９．２７± ２．０４（ｍｇ·Ｌ－１）＊ｈ。４８ｈ尿药累积排泄百分率分别为 ７６．８２％± ６．９２％和 ７５．４５％± ８．２１％。经计算试验制剂（国产）对于参比制剂（进口）的平均相对生物利用度ＡＵＣ０－ｔ；为１００．９８％±１１．５７％，ＡＵＣ０－ ０．６７％ ± ０．５８％。两种片剂的ＡＵＣＯ０－、 ＡＵＣ０－及 Ｃｍａｘ经对数转换后多因素方差分析结果显示，周期间及处方间均无显著性差异（

OBJECTIVE:The aim of this research is to study the relative bioavailability of levofloxacin tablet in Chinese healthy volunteers and to evaluate the bioequivalence. METHODS: A single oral dose 200mg of domestic and imported levofloxacin tablets was given to 21 healthy volunteers in a randomized cross-over study. The concentrations of levofloxacin in serum and urine were determined by HPLC. Results: the main pharmacokinetic parameters of two formulations,domestic and imported tablet, were as follows: t1/2b, were 6.14 f 0.46 and 6.24 f 0.48 h; tmax were 0.92 1 0.40 and 0.95 t 0.41 h; Cmax were 2.76 1 0.47 and 2.69 f 0.45 mg.L-1, AUCo-t,were 18.15 1 2.23 and 18.07 1 2.01 mg.L-1, AUCo- were 19.31 1 2.28 and 19.27 1 2.04 mg.L-1, respectively. The 48-hour cumulative urinary excretion rate were 76.82% t 6.92% and 75.45% f 8.21%. The relative bioavailability of AUCo-t and AUCo- were 100.98% I l.57% and 100.67% f 0.58%. The results of ANOVA and two one-sided t test statistical analysis for in AUCo-t、 In AUCo- and in Cmax showed that two formulations were bioequivalent. The 90% confidence interval of AUCo-t and AUCo- were 96.05%-104.95% and 96.20%-104.21%, in the range of 80-125%; Cmax was 95.97%-109.10%, also in the range of 70-143%,so the two tablets were bioequivalent. CONCLUSION: The domestic and imported levofloxacin tablets were bioequivalent.