醋氯芬酸缓释片在犬体内药代动力学及其相对生物利用度研究

Studies on Pharmacokinetics and Relative Bioavailability of Aceclofenac Controlled-Release Tablets in Dogs

目的 :建立了测定犬血浆中醋氯芬酸浓度的HPLC方法 ,研究醋氯芬酸缓释片在犬体内药代动力学及其相对生物利用度。方法 :样品采用正己烷提取 ,HPLC UV法测定 ,紫外检测波长为 2 76nm。流动相 :甲醇 三蒸水 冰醋酸 (77∶2 3∶0 3)组成。流速 1 5ml/min。色谱柱为C18,10 μm ,柱长 30 0mm× 4 6mmI.D .。 结果 :血浆中杂质不干扰样品峰 ,方法的回收率大于 90 % ,最低检测浓度醋氯芬酸为 1 6 5 μg/ml;线性范围为 1 6 5～ 10 0μg/ml。犬单剂量ig 2 0 0mg醋氯芬酸缓释片后 ,估算的末端相半衰期为 6 0 3± 1 95h ,峰时间和峰浓度分别为 5 0± 2 7h和 6 1 36± 2 0 75 μg/ml,MRT为 9 79± 1 71h。其t1/ 2 、tmax、MRT显著大于普通片 (P <0 0 5 ) ,峰浓度显著低于普通片 (P <0 0 5 )。结论 :本文建立的HPLC UV法适合用于醋氯芬酸的临床研究 ;缓释片具有缓释特征 。

AIM:To establish a HPLC method for determination of aceclofenac in dog plasma and to study pharmacokinetics and bioavailability of aceclofenac controlled release tablets in dogs.METHOD:The plasma samples was extracted with n-hexane and determined by HPLC-UV(λ=276nm).Mobile phase was composed of methanol-water-acetic acid(77∶23∶0.3).The flow rate was 1 5 ml/min The column is C 18 ,10μm,300 mm×4 6 mm ID RESULT: The impurities didn't interfere the sample peak The assay exhibited a linear range of 1 65～100 μg/ml The absolute recovery of aceclofenac was larger than 90% After oral administration of a single dose,the pharmacokinetic parameters of aceclofenac were:t 1/2 6 03±1 95 h,t max 5 0±2 7 h,c max 61 36±20 75 μg/ml,MRT 9 79±1 71 h The aceclofenac controlled release tablet parameters of t 1/2 ,t max and MRT were significantly higher than common tablet(P<0 05) c max was lower than common tablet(P<0 05) CONCLUSION:The method of HPLC-UV established can be used for clinical study of aceclofenac The controlled-release tablets show controlled release profile and bioequivalence in absorption level to common tablets