Du Xiaoli, Li Chonghua, Kuti Joseph L, Nightingale Charles H, Nicolau David P
Center for Anti-infective Research and Development, Hartford Hospital, 80 Seymour Street, Hartford, CT 06102, USA.
J Clin Pharmacol. 2006 Jan;46(1):69-75. doi: 10.1177/0091270005283283.
Meropenem is a highly potent carbapenem antibiotic against gram-positive and gram-negative bacteria. Meropenem plasma concentration data from 99 pediatric patients (aged 0.08-17.3 years) were used to develop a population pharmacokinetic model. Pharmacokinetic analysis was performed using NONMEM with exponential interindividual variability and combinational residual error model. A 2-compartment model was found to fit the data best. Creatinine clearance and body weight were the most significant covariates explaining variabilities in meropenem pharmacokinetics among pediatric patients. The validated final model was used to predict meropenem plasma concentrations in 37 pediatric meningitis patients, receiving 40 mg/kg meropenem, who had minimum inhibitory concentration values of the causative pathogens and outcome available. Since the causative pathogens in all patients were eradicated, no break points for required exposure could be found. The microbiological outcomes indicate that the current clinical dosage regimen provides sufficient drug exposure to eradicate the pathogens commonly involved in pediatric meningitis.
美罗培南是一种对革兰氏阳性菌和革兰氏阴性菌均有高效抗菌活性的碳青霉烯类抗生素。利用99例儿科患者（年龄0.08 - 17.3岁）的美罗培南血浆浓度数据建立了群体药代动力学模型。采用NONMEM进行药代动力学分析，模型包含个体间指数变异和组合残差误差模型。结果发现二室模型最能拟合数据。肌酐清除率和体重是解释儿科患者中美罗培南药代动力学变异性的最显著协变量。经验证的最终模型用于预测37例接受40mg/kg美罗培南治疗的儿科脑膜炎患者的美罗培南血浆浓度，这些患者的致病病原体最低抑菌浓度值及转归情况均已知。由于所有患者的致病病原体均被根除，因此无法确定所需暴露量的折点。微生物学结果表明，当前的临床给药方案可提供足够的药物暴露量以根除儿科脑膜炎常见的病原体。
