健康志愿者中两种不同剂型环丙沙星片的生物等效性评价。

Bioequivalence evaluation of two different formulations of ciprofloxacin tablets in healthy volunteers.

作者信息

Hassan Y, Alfadly S O, Azmin M N, Peh K K, Tan T F Y, Noorizan A A, Ismail O

机构信息

Centre for Bioequivalence Study, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Penang, Malaysia.

出版信息

Singapore Med J. 2007 Sep;48(9):819-23.

PMID:17728962

Abstract

INTRODUCTION

A bioequivalence study of two oral formulations of 500 mg tablets of ciprofloxacin (RAZA Pharmaniaga, Malaysia) as test and Ciprobay (Bayer AG, Germany) as reference, was carried out in 24 healthy human volunteers. Each volunteer received a single dose of ciprofloxacin.

METHODS

The study method used was a double-blind, two-period, two-treatment, two-sequence, and crossover randomised design. Blood samples were taken before, and within 24 hours after drug administration. Plasma concentrations of ciprofloxacin were determined by a high-performance liquid chromatographic method with ultraviolet detection. The pharmacokinetic parameters, C(max) and T(max), were obtained directly from plasma data, k(e) was estimated by log-linear regression, and the area under the curve (AUC) was calculated by the linear trapezoidal rule. The parameters, AUC(0-infinity) and C(max), were tested for bioequivalence after log-transformation of data, while the differences of T(max) were evaluated nonparametrically.

RESULTS

When AUC(0-infinity) and C(max) were analysed using analysis of variance, no statistically significant difference was observed between the two different formulations. The 90 percent confidence intervals of the mean values for the test/reference ratios were 0.95-1.07 for AUC(0-infinity) and 0.90-1.07 for C(max), respectively. Both of these values were within the bioequivalence acceptance range of 0.80-1.25.

CONCLUSION

We found that both formulations are bioequivalent and, therefore, interchangeable.

摘要

引言

在24名健康人类志愿者中开展了一项生物等效性研究，以马来西亚RAZA Pharmaniaga公司生产的500毫克环丙沙星片剂作为试验制剂，德国拜耳公司生产的拜复乐（Ciprobay）作为参比制剂。每名志愿者接受单剂量的环丙沙星。

方法

所采用的研究方法为双盲、两周期、双处理、双序列和交叉随机设计。在给药前及给药后24小时内采集血样。采用带紫外检测的高效液相色谱法测定血浆中环丙沙星的浓度。药代动力学参数C(max)和T(max)直接从血浆数据中获得，k(e)通过对数线性回归估算，曲线下面积（AUC）通过线性梯形法则计算。对数据进行对数转换后，对参数AUC(0-∞)和C(max)进行生物等效性检验，而对T(max)的差异进行非参数评估。