注射用头孢替坦二钠健康人体药动学研究

Pharmacokinetics of Cefotetan for Injection in Healthy Volunteers

目的 研究注射用头孢替坦二钠在中国健康人体内的药动学。方法 12名健康志愿者,男女各半,平行法分别静脉滴注单剂量注射用头孢替坦二钠0.50、1.00和2.00 g,采用离子对反相色谱法测定头孢替坦二钠的经时血药浓度和尿药浓度,使用DAS软件估算药动学参数。结果 单剂量静脉滴注注射用头孢替坦二钠0.50、1.00和2.00 g的主要药动学参数：ρmax分别为（67.93±9.04）,（151.7±12.08）和（263.8±30.35）mg·L-1;AUC0-∞分别为（229.0±18.35）,（459.2±30.23）和（889.6±94.35）mg·h·L-1;而t1/2和MRT均不随剂量改变;0~24 h的尿药累积排泄率分别为（51.10±11.05）%,（62.29±16.36）%和（66.12±16.78）%。结论 建立的头孢替坦二钠血浆和尿液样品离子对反相色谱测定法专属灵敏,适于人体药动学研究。0.50~2.00 g内单次静脉滴注注射用头孢替坦二钠,在中国人体内呈线性药动学特征,男女无差异。

OBJECTIVE To investigate the pharmacokinetics of cefotetan for injection in Chinese healthy volunteers. METH- ODS Twelve volunteers （6 men and 6 women） were intravenously infused with single dose of 0. 50,1.00 and 2. 00 g cefotetan for in- jection, respectively. The plasma and urine concentration of eefotetan was determined by an ion-pairing reversed-phase HPLC method. The pharmacokinetic parameters were calculated by DAS software. RESULTS The main pharmacokinetic parameters found for 0. 50, 1.00 and 2. O0 g cefotetan for injection were as follows, respectively： Pmax （67. 93 ±9. 04）, （151. 7 ±12. 08） and （263. 8 ±30. 35） mg · L-1 ;AUC0-∞ （229.0 ± 18.35） ,（459.2 ±30. 23） and （889. 6 ±94. 35） mg · h · L-1 , while the tl/2 and MRT did not change obviously with the doses. The accumulative excretion rate of cefotetan through urine in 24 h was （51.10 ± 11.05 ）% , （62.29 ± 16.36） % and （66. 12 ± 16. 78） % , respectively. CONCLUSION The established ion-pairing reversed-phase HPLC method is spe- cific, sensitive and suitable for pharmacokinetic study of cefotetan in viva. Linear pharmacokinetics is found for eefotetan in Chinese healthy volunteers after iv infusion in the dose range studied from 0. 50 to 2. 00 g without obvious gender differences.