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首页> 外文期刊>European journal of clinical pharmacology >Pharmacokinetic modelling of cefotaxime and desacetylcefotaxime--a population study in 25 elderly patients.
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Pharmacokinetic modelling of cefotaxime and desacetylcefotaxime--a population study in 25 elderly patients.

机译：头孢噻肟和去乙酰头孢噻肟的药代动力学模型-一项针对25位老年患者的人群研究。

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OBJECTIVE: To develop a pharmacostatistical model to simultaneously characterise the pharmacokinetics of cefotaxime and its main metabolite, desacetylcefotaxime, in elderly patients. METHODS: Cefotaxime, 1 g, was infused three times daily to 25 elderly patients, 66-93 years old. Cefotaxime and desacetylcefotaxime plasma concentrations (289 and 304 samples, respectively), along with demographic and physiological characteristics, were analysed using a population approach. RESULTS: Cefotaxime pharmacokinetics was best described by a two-compartment open model in which desacetylcefotaxime was produced from the central compartment. The final parameter estimates were derived from simultaneous fit of parent/metabolite data. Cefotaxime clearance, mean 5.5 l/h, was positively influenced by body weight and serum protein concentration and negatively influenced by serum creatinine and age. In contrast, desacetylcefotaxime elimination was only decreased by age. The mean terminal half-lives of cefotaxime and desacetylcefotaxime were 1.7 h and 2.6 h, respectively. The stability and predictive performance of the final population pharmacokinetic model was assessed using 200 bootstrap samples of the original data. CONCLUSION: Cefotaxime and desacetylcefotaxime elimination decreased with increasing age above 60 years. This decreased elimination was related to individual characteristics that are typically related to renal function.
机译：目的：建立一种药代统计模型，以同时表征头孢噻肟及其主要代谢产物去乙酰头孢噻肟在老年患者中的药代动力学。方法：每天向25名66-93岁的老年患者输注头孢噻肟1 g，共3次。使用人口方法分析了头孢噻肟和去乙酰头孢噻肟的血浆浓度（分别为289个样品和304个样品）以及人口统计学和生理学特征。结果：头孢噻肟的药代动力学最好用两室开放模型描述，其中从中央室产生去乙酰头孢噻肟。最终参数估计值来自父/代谢物数据的同时拟合。头孢噻肟清除（平均5.5 l / h）受到体重和血清蛋白浓度的正影响，而受血清肌酐和年龄的负面影响。相反，去乙酰头孢噻肟的消除仅随年龄而减少。头孢噻肟和去乙酰头孢噻肟的平均终末半衰期分别为1.7 h和2.6 h。使用原始数据的200个自举样本评估了最终群体药代动力学模型的稳定性和预测性能。结论：随着年龄的增长，头孢噻肟和去乙酰头孢噻肟的消除作用随年龄的增加而降低。减少的消除与通常与肾功能有关的个体特征有关。

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