基于生理药代动力学模型对头孢唑林钠的研究和评价

Evaluation on the efficacy of cefazolin sodium based on physiological pharmacokinetic models

目的基于生理药代动力学理论模型研究方法对头孢唑林钠的有效性水平进行研究和评价。方法建立头孢唑林钠的生理药代动力学模型并根据文献数据进行验证,计算相应组织器官中的药物浓度-时间曲线(简称“药时曲线”),结合本品种的抑菌活性特征,采用相应的评价参数以各器官中药时曲线为依据进行有效性研究与评价,并对其影响因素进行讨论。结果单次静脉注射头孢唑林钠0.5、1.0和4.0 g,药时曲线的模型计算与文献结果间决定系数(r2)为分别为0.863、0.933和0.905,曲线下面积(AUC0-t)预测与文献结果的比值依次为101.1%、108.3%和105.3%,模型与实测结果一致;分别计算静脉注射给药1.0 g、8 h给药间隔方案下头孢唑林钠在肺、心、肾、皮肤和生殖系统中的药时曲线,分别与肺炎链球菌、溶血链球菌、金黄色葡萄球菌、大肠杆菌、奇异变形杆菌等致病菌所对应的最低抑菌浓度(MIC)进行比较,得到在不同器官中对相应病原菌18.7%~99.7%的有效性水平结果。结论头孢唑林钠的生理药代动力学模型可以用于描述药物在人体内的药代动力学过程,适用于抗感染药物的有效性评价,结合细菌对抗感染药物敏感性的结果,利用本研究方法根据治疗目的调整给药方案,获得更好的有效性水平。

Objective To research and evaluate the efficacy of cefazolin sodium based on physiological pharmacokinetic models.Methods Physiologically based pharmacokinetic(PBPK)model of cefazolin was established using software and then further validated with the data collected from literatures.Plasma concentration-time curves in corresponding tissues and organs were calculated.Treatment efficacy was evaluated based on the plasma concentration-time curves in relevant organs with specific parameters.Those factors which have influence on the efficacy were also discussed meanwhile.Results For the single intravenous administration of cefazolin by 0.5,1.0 and 4.0 g.The determining factor(r2 values)of the results of model established and actual measurement with literature data were 0.8630.933 and 0.905.The rates of model established and actual measurement of the corresponding average value of the area under the curve(AUC0-t)were 101.1%108.3%and 105.3%.Further calculation shown the effectiveness of lung,heart,kidney,skin and reproductive system with minimum inhibitory concentration of streptococcus pneumoniae,streptococcus haemolyticus,staphylococcus aureus,escherichia coli and roteus mirabilis were 18.7%~99.7%.Conclusion The PBPK model of cefazolin preparations can be described the pharmacokinetic of drugs in human,it is suitable for the efficacy evaluation of anti-infective drugs.Combined with the susceptibility test of antibiotics results,to achieve the better effectiveness by adjust the plan according to the treatment purpose.