摘要
目的建立巴马小型香猪的药物代谢研究模型,了解巴马小型香猪机体对药物的作用.方法选择抗动脉粥样硬化的HMG-CoA还原酶抑制剂型药物洛伐他汀（LV）为模型药,给6月龄雄性巴马小型香猪二组共8头,单剂量（6.0 mg/kg,2.4 mg/kg）灌胃,采用RP-HPLC法检测LV的血药浓度,并计算药代动力学参数.结果 LV在巴马小型香猪的处置符合一室开放模型;Tmax分别为（2.54±0.18）,（2.82±0.44）h;T1/2α分别为（1.53±0.05）,（1.52±0.44）h;T1/2β分别为（2.04±0.32）,（2.77±0.89）;Cmax分别为（28.86±3.76）,（10.93±1.77）ng/mL;AUC分别为（202.76±41.98）和（104.86±16.44）（ng/mL）×h.结论 LV在巴马小型香猪的吸收速度约为正常人的0.5倍,消除速度为正常人的1.5～2倍,但整个代谢过程类似正常人,均属一室开放模型,提示巴马小型香猪可作为心血管系统药物LV药代研究的良好模型.
Objective To study the characteristics of lovastatin （LV） pharmacokinetics in Bama minipig. Methods The plasma concentration of LV in 3 of 6-month old male Bama minipigs orally administered in a dose of 6 mg/mL and 5 of 6-month old male Bama minipigs in a dose of 2.4 mg/mL was detected by high-performance liquid chromatography. Results The pharmacokinetic parameters suggested that one-compartment model was found in all groups after oral administration of LV. In minipigs treated with LV in a dose of 2.4 mg/mL and 6.0mg/mL, the peak time（Tmax）was（2.54 ±0.18）h and （2.82 ± 0.44） h, respectively; T1/2α was（1 .53 ± 0.05）h and（1.52 ± 0.44）h, respectively; T1/2β was（2.04 ± 0.32）h and（2.77± 0.89） h, respectively ; Cmax was （28.86 ± 3.76）ng/mL and （ 10.93 ± 1.77） ng/mL, respectively; AUC was（202.76 ± 41.98）ng/mL at one hour and（104.86 ±16.44） ng/mL at one hour, respectively. Conclusion Our findings showed that both Bama minipig and human have the same one-compartment model, but the absorption time of IV in Bama minpigs was 0.5 times slower than in humans while elimination time of LV in Bama minipigs was 1.5 ～ 2 times shorter than in humans. Those data support that Bama minipig is a good model for study on pharmacokineties of lovastatin.
出处
《中国比较医学杂志》
CAS
2006年第3期139-141,共3页
Chinese Journal of Comparative Medicine
基金
国家"十五"科技攻关计划重点项目课题资助(2004BA717B)
