Shohag M Hasanuzzaman, Islam Mohammad Safiqul, Ahmed Maizbha Uddin, Joti Jafreen Jamal, Islam M Siddiqul, Hasanuzzaman M, Hasnat Abul
Department of Clinical Pharmacy and Pharmacology, University of Dhaka, Dhaka, Bangladesh.
Arzneimittelforschung. 2011;61(11):617-21. doi: 10.1055/s-0031-1300564.
The aim of this study was to compare the pharmacokinetic properties of two etoricoxib (CAS 202409-33-4) 60 mg formulations, namely Etocox-60 (test product) and reference product, and to evaluate whether these two formulations meet the FDA criteria to assume bioequivalence. Twenty-four healthy volunteers were enrolled into this randomized, single-dose, 2-way crossover, open-label pharmacokinetic study. Subjects were randomly assigned to receive the test formulation followed by the reference formulation or vice versa as a single dose of 60 mg tablets after 12 h overnight fasting, with a washout period of two weeks. Following oral administration, blood samples were collected at 0 (baseline), 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0, and 120.0 h. Serum concentration of etoricoxib was assessed using a high performance liquid chromatographic-UV spectrometry procedure. The pharmacokinetic parameters were determined by the non-compartmental method. After administering a single dose of 60 mg of each etoricoxib formulation, the obtained mean (SD) values for the test and reference products were 1.26 (0.33) and 1.29 (0.35) microg/ml for Cmax; 3.25 (2.64) and 2.63 (1.40) h for t(max); 29.63 (8.31) and 30.40 (5.85) h x microg/ml for AUC0-120; and 31.84 (10.97) and 33.00 (8.10) h x microg/ml for AUC0-infinity, respectively. The mean t1/2 was found 27.99 (7.87) h and 29.84 (7.93) h for test and reference product respectively. From paired t-test, no significant differences were observed (p > 0.05) for any pharmacokinetic parameters. After analysis of variance, no period, sequence or formulation effects were observed for any pharmacokinetic property. The 90% confidence intervals of the test/reference mean ratios of the 1n-transformed AUC0-120, AUC0-infinity and Cmax mean values were 95.90% (85.37%-107.74 %), 94.69% (84.43%-106.20%) and 97.87% (85.54 %-111.98 %), respectively, which fell within the predetermined FDA bioequivalence range of 80%-125%. This single-dose study found that the test and reference formulations of etoricoxib met the regulatory criteria for bioequivalence in terms of both rate and extent of absorption.
本研究的目的是比较两种依托考昔（CAS 202409-33-4）60毫克制剂，即Etocox-60（试验产品）和参比产品的药代动力学特性，并评估这两种制剂是否符合美国食品药品监督管理局（FDA）关于生物等效性的标准。24名健康志愿者参与了这项随机、单剂量、两交叉、开放标签的药代动力学研究。受试者在禁食过夜12小时后随机分配接受试验制剂，随后接受参比制剂，或反之，作为60毫克片剂的单剂量给药，洗脱期为两周。口服给药后，在0（基线）、0.5、1.0、1.5、2.0、3.0、4.0、6.0、8.0、10.0、12.0、24.0、48.0、72.0、96.0和120.0小时采集血样。依托考昔的血清浓度采用高效液相色谱-紫外光谱法进行评估。药代动力学参数采用非房室方法测定。给予每种依托考昔制剂60毫克单剂量后，试验产品和参比产品获得的平均（标准差）值分别为：Cmax为1.26（0.33）和1.29（0.35）微克/毫升；t(max)为3.25（2.64）和2.63（1.40）小时；AUC0-120为29.63（8.31）和30.40（5.85）小时×微克/毫升；AUC0-无穷大为31.84（10.97）和33.00（8.10）小时×微克/毫升。试验产品和参比产品的平均t1/2分别为27.99（7.87）小时和29.84（7.93）小时。配对t检验结果显示，任何药代动力学参数均未观察到显著差异（p>0.05）。方差分析后，未观察到任何药代动力学特性存在周期、序列或制剂效应。1n转换后的AUC0-120、AUC0-无穷大和Cmax平均值的试验/参比平均比值的90%置信区间分别为95.90%（85.37%-107.74%）、94.69%（84.43%-106.20%）和97.87%（85.54%-111.98%），均落在FDA预先规定的80%-125%生物等效性范围内。这项单剂量研究发现，依托考昔的试验制剂和参比制剂在吸收速率和程度方面均符合生物等效性的监管标准。
