头孢三嗪噻肟与头孢氨噻肟在中国健康成人中多次给药...

MULTIPLE-DOSE PHARMACOKINETICS OF CEFTRIAXONE AND CEFOTAXIME IN CHINESE HEALTHY ADULTS

本项研究目的是比较头孢土嗪噻肟(ceftriaxone,CTRX)临床常用的几种每日单次给药方案与作者建议的每日2次给药方案进行比较,并在研究比较的基础上提出2种治疗方案供临床参考。多次给药的血药浓度可以在单次给药的药代动力学参数的基础上,用电脑进行计算,并可根据药物在体内的时间过程与血浆浓度、治疗反应及其他因素(消除半衰期、血浆蛋白结合率等)之间的相互关系对适宜的剂量方案进行评价。按照我们先前对CTRX与CTX所进行的单次给药药代动力学比较研究,用其中静脉给药的药代动力学参数。利用IBM PC/AT电脑,估算出10种多次给药的给药方案。所用程序由中国科学院数学研究所提供。从10种方案中选出一种比较合理的方案B-1,在6名中国男性成人志愿者中进行多次给药药代动力学研究。研究结果表明:在为期5天的疗程内,静脉给药10次,所得药代动力学参数与电脑估算结果非常相似。实测与估算的药代动力学参数表明:CTRX多次给药后各次血药浓度均明显高于CTX,与单次给药药代动力学研究结果相符。作者建议的二种治疗方案为: B-1 用于中度感染:最初48h,1g q12h×2d。第3—7天,0.5g q12h×5d。B-2 用于重度感染:最初48h,每12h给药1次,第1次2g,第2次1g。第3—7天,每日2次,每次1g,间隔12h。

The purpose of this study was to compare serum levels ofceftriaxone among those regimens commonly used in clinic for the trea-tment of moderate severe infections. and the two regimens recommendedby the anthors.The serum levels of a drug following multiple doses canbe estimated by the computer based on the pharmacokinetic parametres ob-tained from the single dose pharmacokinetic study, and the proper dosingregimen can then be evaluated in terms of the resultant time course ofthe drug in the body and the known relationship among the plasma level,therapeutic response and other factors (elimination half life, protein bin-ding rate, etc.) of the drug. According to our previous study on the phar-mackinetics of ceftriaxone and cefotaxime following a single dose admin-istered intravenously, ten regimens have been estimated by using IBM PC/AT with a program provided by the Institute of Mathematics. One of theregimens considered more reasonabley than the other regimens commonlyused in clinic for the treatment of moderate severe infections. Thereforea multiple-dose pharmacokinetic study was performed in six Chinese malehealthy adults. The results showed. that the pharmacokinetic data of cef-triaxone after ten doses administered intravenously in 5 days were verysimilar to the estimated data calculated by the computer, and the serumlevels of ceftriaxone were much higher than those of cefotaxime. The pro-posed regimens were as follows: Regimen-1: for the treatment of moderate severe infections: first 48 h lg q 12h×2 days, 3rd-7th day 0.5 g q 12h×5 days Regimen-2: for the treatment of severe infections: first 48 h 2g followed by lg with an interval of 12h×2 days 3rd-7th day 1g q 12h×5 days