TAP-HP-β-CD包合物在体外释药和鸡体内的药动学研究

The Release of TAP-HP-β-CD Inclusion in vitro and Pharmacokinetics in Chickens

[目的]研究甲砜霉素-羟丙基-β-环糊精(TAP-HP-β-CD)包合物的体外释药和鸡体内的吸收动力学特性。[方法]以甲砜霉素(TAP)原料药为对照药,采用小杯法测定TAP-HP-β-CD包合物的累积体外溶出度;将10只三黄鸡分成2组,即试验组和对照组,分别灌服TAP-HP-β-CD包合物和甲砜霉素粉后,分别在给药前、给药后0.08、0.25、0.50、1.00、1.50、2.00、3.00、4.00、6.00、8.00、10.00和12.00h鸡翅静脉采血2ml,取其血浆加入内标氟甲砜霉素,以乙腈提取溶剂,用RP-HPLC内标法检测其不同时间的血药浓度,采用3p87程序计算药物吸收动力学参数。[结果]TAP-HP-β-CD包合物的体外释药速度快,TAP包合物血药浓度达峰时间短、相对生物利用度高。[结论]该研究为TAP新剂型开发与利用提供了科学依据。

[Objective]To study the release of TAP-HP-β-CD inclusion in vitro and pharmacokinetics in chickens.[Method]The accumulated dissolution of TAP-HP-β-CD inclusion in vitro was determined in accordance with the small cup method of Chinese Veterinary Pharmacopoeia（2005 Edition）appendices,meanwhile the raw material of TAP was used as standard comparison.To study the pharmacokinetics of TAP-HP-β-CD inclusion in vivo,a total of 10 Three-yellow chickens were divided into two groups randomly and the blood samples of chickens were collected before administration and at 0.08,0.25,0.50,1.00,1.50,2.00,3.00,4.00,6.00,8.00,10.00 and 12.00 h after the oral administration of TAP-HP-β-CD and TAP powder respectively.The blood concentrations of TAP at different time were determined by the RP-HPLC internal standard method after the chicken plasma containing florfenicol as the internal standard.The pharmacokinetic parameters were calculated and analyzed by 3p87 pharmacokinetic program.[Result] The release rate of TAP-HP-β-CD inclusion was faster in vitro,and the time to reach the peak level was shorter and the relative bioavailability was greatly enhanced.[Conclusion] This study provide a scientific basis for the development and utilization of novel TAP dosage forms.