Sánchez-Navarro A, Colino C I, Sánchez Recio M M
Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Salamanca, Spain.
Clin Pharmacokinet. 2001;40(2):125-34. doi: 10.2165/00003088-200140020-00004.
To analyse the relationship between a series of estimated pharmacokinetic-pharmacodynamic parameters and the reported efficacy of ceftizoxime.
Retrospective literature search and analysis using different correlation models.
The following parameters were calculated for each group of patients included in the study from the simulated plasma concentration curves corresponding to the dosage regimen administered: (i) peak concentration at steady state divided by the minimum inhibitory concentration (CmaxSS/MIC); (ii) the time that the plasma drug concentration exceeded the MIC scaled to 24 hours at steady state [(tSS)24h > MIC]; (iii) the total area under the concentration-time curve over 24 hours at steady state divided by the MIC [(AUC(SS))24h/MIC]; and (iv) the AUC at steady state for the period of time that the concentration is above the MIC over a period of 24 hours divided by the MIC [(AUIC(SS))24h]. A univariate correlation analysis was performed considering efficacy [rate (%) of clinical cure or bacterial eradication] as the dependent variable and the pharmacokinetic-pharmacodynamic parameter as the independent variable, using linear and nonlinear models.
(tSS)24h > MIC was the only parameter that was statistically correlated with efficacy, the linear model being the best choice among the 4 relationship approaches tested. A biased frequency distribution of reported efficacy data constricts the correlation analysis to a narrow range of efficacy and hinders interpretation of the results.
The reporting of cases with low efficacy rates as well as those with high efficacy rates, including information on patient idiosyncrasies and the infecting organisms, would be of great help in performing retrospective analyses of the use of antimicrobial agents, leading to the optimisation of therapy with this type of drug in clinical practice.
分析一系列估算的药代动力学-药效学参数与头孢唑肟报告的疗效之间的关系。
使用不同的相关模型进行回顾性文献检索和分析。
根据给药方案对应的模拟血浆浓度曲线，为纳入研究的每组患者计算以下参数：(i)稳态时的峰浓度除以最低抑菌浓度（CmaxSS/MIC）；(ii)稳态时血浆药物浓度超过MIC的时间按24小时进行换算[(tSS)24h > MIC]；(iii)稳态时24小时浓度-时间曲线下的总面积除以MIC[(AUC(SS))24h/MIC]；以及(iv)稳态时浓度高于MIC的24小时时间段内的AUC除以MIC[(AUIC(SS))24h]。以疗效[临床治愈或细菌清除率(%)]为因变量，药代动力学-药效学参数为自变量，采用线性和非线性模型进行单变量相关分析。
(tSS)24h > MIC是唯一与疗效具有统计学相关性的参数，线性模型是所测试的4种关系方法中的最佳选择。报告的疗效数据存在偏态频率分布，将相关分析限制在较窄的疗效范围内，阻碍了结果的解释。
报告低疗效率和高疗效率的病例，包括患者特异性和感染病原体的信息，将有助于对抗菌药物的使用进行回顾性分析，从而在临床实践中优化这类药物的治疗。
