比阿培南的人体药动学

Pharmacokinetics of single and multiple oral doses of biapenem in healthy volunteers

目的:建立人血浆中比阿培南的高效液相检测方法,研究健康受试者静脉滴注比阿培南后的药动学。方法:血浆样品用72%的高氯酸沉淀,色谱柱为Hypersil C18柱(250mm×4.6mm,5μm),流动相为乙腈-0.05mol.L-1磷酸二氢钾(27∶73);流速为1.0mL.min-1;检测波长为300nm,采用外标法定量。单剂量与多剂量给药后比阿培南血药浓度数据采用DAS药动学软件计算药动学参数。结果:比阿培南单剂量与多剂量给药后主要药动学参数分别为t1/2为(1.23±0.24)h和(1.17±0.31)h,AUC0→τ为(40.7±13.5)mg.L-1.h和(41.1±16.3)mg.L-1.h。结论:HPLC法测定血浆中比阿培南浓度灵敏度高,操作简便、快速;比阿培南连续给药后药物在体内蓄积不明显。

OBJECTIVE To establish a sensitive and selective HPLC method for the determination of biapenem in human plasma and study the pharmacokinetics of biapenem in healthy volunteers after single and multiple administrations. METHODS The plasma samples were treated by protein precipitation with 72% perchloric acid. Separation was achieved on a Hypersil C18 reversed-phase column with a mobile phase composed of acetonitrile- 0. 05M dibasic potassium phosphate buffer （27：73）. The UV detection was carried out at 300 um and the flow rate was 1.0 mL·min^-1. The pharmacokinetics parameters were calculated with software DAS. RESULTS The pharmacokinetics parameters of biapenem from single-dose and multiple-dose expriments were as follows： t1/2 were （1.23 ± 0. 24） hand（1.17±0.31）h,AUC0→ι were （40.7±13.5）mg·L^-1·h and （41.1±16.3）mg·L^-1·h, respectively. CONCLUSION This method was robust and suitable for clinical pharmacokinetic studies of biapenem. The results suggested that there was no accumulation of biapenem in plasma to be found after the repeated administration.