双氯芬酸钾缓释片在家犬体内的药动学及生物等效性研究

 目的对自制双氯芬酸钾缓释片和市售双氯芬酸钾普通片进行家犬体内的生物等效性评价。方法6条家犬按标准的2×2交叉试验方案设计,禁食12 h后空腹口服普通片剂(参比制剂)50 mg或缓释片剂(供试制剂)75 mg;采用RP-HPLC紫外检测法检测血浆中药物浓度,并计算相关的药动学参数,判定两制剂是否生物等效。结果参比制剂及供试制剂的主要药动学数据如下:t_max分别为(0.50±0.01)和(4.17±0.10)h;ρ_max分别为(4.96±1.06)和(1.37±0.11)mg·L^-1;AUC_0～∞分别为(9.09±0.89)和(12.86±0.70)mg·h·L^-1;t_1/2分别为(2.33±0.84)和(7.94±1.45)h。结论两种制剂的主要药动学参数ρ_max和AUC_0～∞经对数转换后进行方差分析及双单侧t检验,并计算90%置信区间,表明两种制剂为以AUC为评价指标的生物等效制剂,相对生物利用度为97.16%,供试制剂与参比制剂相比具有良好的缓释效果。

Study on Pharmacokinetics and Bioequivalence of Diclotenac Potassium Sustained-Release Tablets in Dogs

OBJECTIVE To study the bioequivalence of diclotenac potassium sustained-release tablets and commercial tablets in dogs.METHODS 50 mg commercial tablet(reference)and 75 mg diclotenac potassium sustained-release tablet(test)were given to 6 healthy male dogs in a randomized two-way crossover design,respectively.The concentrations of diclotenac potassium were determined by RP-HPLC with UV detection.RESULTS The pharmacokinetic parameters of diclotenac potassium of commercial tablets and sustained-release tablets were as following:t_max(0.50±0.01) and(4.17±0.10) h;ρ_max(4.96±1.06)and(1.37±0.11) mg·L^-1;AUC_0～∞(9.09±0.89) and(12.86±0.70)mg·h·L^-1;t_1/2(2.33±0.84) and(7.94±1.45) h,respectively.The mean relative bioavailability of diclotenac potassium sustained-release tablets vs commercial tablets was 97.16%.CONCLUSION The two formulations are bioequivalent,regarding the estimate of AUC.The test formulation has more significant sustained-release effect than the reference formulation.