诺氟沙星片在中国健康受试者空腹和餐后状态下生物等效性研究#br#

目的：采用随机、开放、两周期、自身交叉、单次给药试验设计比较浙江医药股份有限公司新昌制药厂生产的诺氟沙星片与原研产品BACCIDAL在中国健康人体中的生物利用度，并评价两种制剂的生物等效性。方法：分别在空腹和餐后条件下，健康受试者随机交叉单剂量口服诺氟沙星片受试制剂或参比制剂100 mg，采用液相色谱-质谱串联（LC-MS/MS）法测定受试者服药前后不同时间点血浆内药物浓度，采用WinNonlin 7.0软件计算主要药代动力学参数，并评价两种制剂的生物等效性。结果：空腹试验共有28例受试者入组并完成试验，诺氟沙星受试制剂与参比制剂的Cmax分别为（607.62±125.24）ng/mL和（552.01±134.11）ng/mL；AUC0-t分别为（2 551.66±509.08）ng·mL-1·h和（2 429.98±460.47）ng·mL-1·h；AUC0-∞分别为（2 675.40±523.04）ng·mL-1·h和（2 557.68±485.43）ng·mL-1·h；t1/2分别为（6.07±0.69）h和（6.18±0.92）h；两种制剂的Cmax、AUC0-t和AUC0-∞几何均值比的90%置信区间分别为101.45%～121.94%、98.96%～111.27%、98.82%～110.76%。餐后试验共有28例受试者入组并完成试验，诺氟沙星受试制剂与参比制剂的Cmax分别为：（256.54±58.87）ng/mL和（300.80±94.67）ng/mL；AUC0-t分别为（1 314.74±349.92）ng·mL-1·h和（1 278.60±314.77）ng·mL-1·h；AUC0-∞分别为（1 413.73±361.98）ng·mL-1·h和（1 374.98±321.62）ng·mL-1·h；t1/2分别为（6.66±1.23）h和（6.66±1.34）h；两种制剂的Cmax、AUC0-t和AUC0-∞几何均值比的90%置信区间分别为81.42%～93.56%、99.61%～105.58%、99.80%～105.21%。结论：浙江医药股份有限公司新昌制药厂生产的诺氟沙星片与原研产品BACCIDAL在中国健康受试者空腹和餐后服用的状态下等效且安全性良好，临床上可以替换使用。

Bioequivalence of norfloxacin tablets in Chinese Healthy volunteers under Fasting and Fed Condition

AIM: To compare the bioavailability of norfloxacin tablets produced by Zhejiang Pharmaceutical Co., Ltd with the original product BACCIDAL, and to evaluate bioequivalence of two formulations, a randomized, open, two-cycle, self-crossing trial in healthy Chinese population was designed. METHODS: Under fasting and fed conditions, healthy volunteers were given a single dose of norfloxacin test or reference tablets for 100 mg. Liquid chromatography-mass spectrometry (LC-MS/MS) method were used to determine drug concentration in the plasma taken at different time points before and after dosing. Pharmacokinetic parameters and the bioequivalence of the two formulations were calculated by WinNonlin 7.0 software. RESULTS: A total of 28 healthy volunteers were enrolled and completed the fasting test. The pharmacokinetic parameters for test and reference preparations in fasting state were as follows: Cmax were (607.62±125.24) ng/mL and (552.01±134.11) ng/mL; AUC0-t were (2 551.66±509.08) ng·mL-1·h and (2 429.98±460.47) ng·mL-1·h; AUC0-∞ were (2 675.40±523.04) and (2 557.68±485.43) ng·mL-1·h, t1/2 were (6.07±0.69) and (6.18±0.92) h. The 90% confidence intervals of the geometric mean ratio of Cmax, AUC0-t and AUC0-∞ for the test and reference preparations of norfloxacin tablets taken by healthy volunteers under fasting condition were 101.45%-121.94%, 98.96%-111.27% and 98.82%-110.76%. The pharmacokinetic parameters for test and reference preparations in fed state were as follows: Cmax were (256.54±58.87) and (300.80±94.67) ng/mL; AUC0-t were (1 314.74±349.92) and (1 278.60±314.77) ng·mL-1·h; AUC0-∞ were (1 413.73±361.98) and (1 374.98±321.62) ng·mL-1·h, t1/2 were (6.66±1.23) and (6.66±1.34) h. The 90% confidence intervals of the geometric mean ratio of Cmax, AUC0-t and AUC0-∞ for the test and reference preparations of norfloxacin tablets taken by healthy volunteers under fed condition were 81.42%-93.56%, 99.61%-105.58% and 99.80%-105.21%. CONCLUSION: The test preparation of norfloxacin tablets and the reference preparation are bioequivalent, and they can be used interchangeably clinically.