吡罗昔康包合物的体内药动学与胃刺激性研究-第三军医大学学报.DOC

吡罗昔康包合物摘要: 目的 吡罗昔康包合物Beagle 。方法 Beagle HPLC法测定吡罗昔康血浆浓度，用统计矩原理进行血药浓度－时间数据分析。结果 0.89±0.09小时和3.92±0.49小时，两者有显著性差异（P＜0.01），两者的半衰期t1/2分别为31.30±4.38小时和29.38±1.83小时，AUC分别为242.92±30.04μg·h·mL-1和230.55±8.06μg·h·mL-1，均无明显差别，吡罗昔康包合物相对于市售片剂的相对生物利用度为106.74%。结论 建立的HPLC分析方法准确可靠。 关键词：β-环糊精；包合物；药动学；生物等效性 Study on pharmacokinetics of piroxicam-β-cyclodextrin inclusion complexes in beagle dogs ABSTRACT: OBJECTIVE To study the pharmacokinetics of piroxicam-β-cyclodextrin inclusion complexes in beagle dogs. METHODS An open randomized two-period crossover self control trial was conducted to beagle dog. Piroxicam in plasma was assayed by HPLC after a single oral dose of 20 mg both for test and reference tablets. The serum concentration-time data were analyzed by non-compartmental model. RESULTS The tmax of the capsules and the tablets were 0.89?.09 hours and 3.92?.49 hoursth，respectively，the former was significantly smaller than the latter; The t1/2 were 31.30±4.38 hours and 29.38±1.83 hours, respectively; The AUC were 242.92±30.04μg·h·mL-1 and 230.55±8.06μg·h·mL-1 , respectively. Both of them had no significant difference. The relative bioavailability of capsules was 106.74% compared to tablets.. CONCLUSIONS The established HPLC method is accurate and reliable．The two ptablets are bioequivalent. The capsules significantly accelerated the dissolution and absorption rate. KEY WORDS: piroxicam; β-cyclodextrin; inclusion complex; pharmacokinetics; bioavailability 作者简介 张建明（男），主管药师.E-mail：sayzjm@ *通讯作者：方晓玲，.E-mail：xlfang@ 非甾体抗炎药吡罗昔康（piroxicam）具有很强的抗炎作用，临床用于治疗风湿性和类风湿性关节炎，药物分子具有良好的膜渗透性，口服吸收良好。但是由于其在水中难溶，因此在胃肠液中溶解速度很低，继而导致吸收缓慢和起效时间延迟。据文献报道，将吡罗昔康制成β-环糊精(-CD)包合物能加快其吸收速度[1-4]，降低胃肠道刺激性[5-7]。本文拟考察自制吡罗昔康包合物在Beagle犬体内的药物动力学过程，以期为新制剂的研发提供参考。 1、仪器和材料仪器 LC-10A型高效液相色谱仪，SPD-10A型紫外可见检测仪（日本岛津公司）HS2000色谱数据工作站（杭州英谱公司）5μm，4.6×150mm色谱柱（公司）药品与试剂 吡罗昔康原料药（200509087，含量98.8%，河南开封制药有限公司）β-环糊精β-环糊精乙腈，色谱纯（TEDIA，TEDIA Company，USA）甲醇，色谱纯（江苏汉邦科技公司）其他试剂均为分析纯 Beagle犬：♀，体重10.35±0.48kg，复旦大学上海医学院实验动物中心提供。 采用随机分组、自身对