抗菌药物药代动力学-药效学模型用于优化五水头孢唑林钠的给药方案

Dosing regimen selection for cefazolin sodium pentahydrate based on its pharmacokinetic/pharmacodynamic analysis

目的探讨五水头孢唑林钠在临床治疗感染疾病中给药剂量的合理性。方法根据静脉滴注五水头孢唑林钠每次0.25-3.0 g,qd、bid、tid、qid等多种给药方案治疗常见致病菌感染的体外抗菌活性实验与Ⅰ期临床药代动力学研究数据进行Monte Carlo模拟（10 000例）,获得的累积反应分数（CFR）,并进行给药方案的比较（以CFR≥90%的给药方案为最佳给药方案）。结果以CFR≥90%的给药方案为最佳给药方案。按bid、tid和qid等不同频率给药,治疗常见致病菌感染所需的每次最低给药剂量分别为1.0 g、0.75 g和0.5 g。结论从注射用五水头孢唑林钠安全性、临床疗效、依从性等方面考虑,针对轻、中度感染患者,给药方案可用1.5-2.0 g,bid,重度感染可增至每次3.0 g或遵医嘱。

Objective To explore the rationality of the used dosage of cefazolin sodium pentahydrate in the treatment of infections. Methods The pharmacodynamic data（MIC） was obtained from the preclinical studies. The pharmacokinetic data from the phase Ⅰ clinical research trials and published protein binding were varied according to lognormal and uniform distributions. A Monte Carlo simulation（10,000 subjects） estimated the cumulative fraction of response（CFR） at f% T MIC = 50%for intravenous cefazolin sodium pentahydrate 0. 25-3. 0 g every 6-24 h. Results With the dosage of CFR≥90% as the optimal dosage regimen,the lowest dosage for treating common infection was 1. 0 g bid,0. 75 g tid and 0. 5 qid,respectively. Conclusion Based on its pharmacokinetic / pharmacodynamic characteristics,safety and cost effect,the appropriate dosing regimen of cefazolin sodium pentahydrate injection was1. 5-2. 0 g every 12 h for mild and moderate infection,for serious infection the dose can increase to 3. 0 g every 12 h or follow doctors＇ advices.