Barthel W, Hüller G, Haustein K O
Clinical Pharmacology Erfurt, Friedrich Schiller University, Germany.
Int J Clin Pharmacol Ther. 1999 Mar;37(3):148-52.
The study was undertaken to prove the bioequivalence of two allopurinol tablet preparations.
SUBJECTS, MATERIALS AND METHODS: The relative bioavailability of allopurinol from two tablet preparations (Uribenz vs. Zyloric 300) was estimated on 18 volunteers of both sexes in an open randomized study by administering one tablet of each preparation at an interval of 2 weeks. The plasma concentrations of allopurinol and its active metabolite oxypurinol were measured over a time-period of 72h by HPLC.
While the mean AUC(0-72) values of allopurinol and oxypurinol after the test and reference preparations are entirely identical (5.33 vs. 5.21 and 137.95 vs. 137.96 microg h ml(-1), respectively), the C(max) values of oxypurinol unlike those of allopurinol show small differences (4.59 vs. 4.78 and 1.91 vs. 193 microg/ml, respectively). According to the parametric and non-parametric analysis, the quotients AUC(T)/AUC(R) and C(maxT)/C(maxR) lie within the confidence intervals 0.8 to 1.2 and 0.7 to 1.3 respectively With regard to the t(max) of allopurinol, the differences of test and reference preparations are between 0.10 to 0.05h and of oxypurinol between -0.10 to 0.87h (parametric analysis). Both, Uribenz 300 and Zyloric 300 caused a maximum decrease of the uric acid concentration in the volunteers by 18% after 10 and 24h, respectively.
Thus the bioequivalence of the allopurinol tablet preparations is demonstrated.
开展本研究以证明两种别嘌醇片剂制剂的生物等效性。
受试者、材料与方法：在一项开放随机研究中，对18名男女志愿者给予两种片剂制剂（优立苯唑与痛风利仙300）各一片，间隔2周给药，以此评估两种片剂制剂中别嘌醇的相对生物利用度。采用高效液相色谱法在72小时的时间段内测定别嘌醇及其活性代谢产物氧嘌呤醇的血浆浓度。
虽然试验制剂和参比制剂后别嘌醇和氧嘌呤醇的平均AUC(0 - 72)值完全相同（分别为5.33对5.21以及137.95对137.96μg·h·ml⁻¹），但氧嘌呤醇的C(max)值与别嘌醇不同，显示出微小差异（分别为4.59对4.78以及1.91对1.93μg/ml）。根据参数分析和非参数分析，AUC(T)/AUC(R)和C(maxT)/C(maxR)的商分别处于0.8至1.2和0.7至1.3的置信区间内。关于别嘌醇的t(max)，试验制剂和参比制剂的差异在0.10至0.05小时之间，而氧嘌呤醇的差异在 - 0.10至0.87小时之间（参数分析）。优立苯唑300和痛风利仙300分别在10小时和24小时后使志愿者体内尿酸浓度最大降幅达18%。
由此证明了别嘌醇片剂制剂的生物等效性。
