普鲁卡因青霉素-硫酸双氢链霉素混悬液在猪体内的药物动力学

Pharmacokinetics of Procaine Penicillin-dihydrostreptomycin Sulfate Suspension in Pigs

健康长白猪7头,按拉丁方试验设计,进行单剂量静脉注射青霉素(20 000单位/kg体重)钠、硫酸双氢链霉素(20 000单位/kg体重)及肌肉注射普鲁卡因青霉素-硫酸双氢链霉素混悬剂(20 000单位/kg体重)的药物动力学研究。HPLC法和HPLC-MS/MS法分别测定血浆中的青霉素和双氢链霉素浓度,WinNonlin软件处理血药浓度-时间数据。静脉注射青霉素钠、硫酸双氢链霉素的药时数据最佳模型为三室开放模型。肌肉注射混悬剂后青霉素G的药时数据符合一级吸收一室模型。主要药物动力学参数:t1/2ka为0.66 h,t1/2β为5.80 h,t(max)为2.3 h,C(max)为1.66 mg/L,AUC为17.65,CL为0.69 L/h.kg,F为70.57%;肌肉注射混悬剂后双氢链霉素数据符合一级吸收二室开放模型,主要药动参数:t1/2ka为0.21 h;t1/2α为2.06 h;t1/2β为8.22 h,t(max)为0.8 h,C(max)为51.42 mg/L,AUC为280.74,F为101.96%。肌肉注射混悬液药物动力学特征为青霉素G吸收迅速,消除缓慢;双氢链霉素吸收迅速完全,消除缓慢,生物利用度高。

The pharmacokinetics of procaine penicillin-dihydrostreptomycin（DHS） sulfate suspension was investigated by a Latin square design following single intravenous administration（20 000 IU/kg） of penicillin,dihydrostreptomycin sulfate,and intramuscular administration（20 000 IU/kg） of procaine penicillin-dihydrostreptomycin sulfate suspension in 7 healthy pigs.The concentrations of penicillin G and DHS in plasma were determined by HPLC and HPLC-MS/MS respectively.A three-compartment open model best described the concentration-time data after single i.v.dosing in the healthy pigs.It＇ s best to fit the penicillin G concentration-time data to one-compartment open model with first order absorption after single i.m.dosing.The main pharmacokinetic parameters were as follows： t1/2ka 0.66 h,t1/2β 5.80 h,t（max） 2.3 h,C（max） 1.66 mg/L,AUC 17.65,CL 0.69 L/h·kg,F 70.57%.A two-compartment model with first order absorption best described the DHS concentration-time data after single i.m.administration in healthy pigs.The main pharmacokinetic parameters were as follows： t1/2ka 0.21h;t1/2α 2.06 h;t1/2β 8.22 h,t（max） 0.8 h,C（max） 51.42 mg/L,AUC 280.74,F 101.96%.The results showed that penicillin G and DHS were both rapidly and completely absorbed and slowly eliminated after i.m.administration of the suspension.