住院病人茶碱群体药物动力学NONMEM法分析

对72名临床病人进行茶碱群体药物动力学研究,用NONMEM法分析了多种因素对茶碱药物动力学过程的影响。结果表明:在18至77a范围内,年龄对清除率(Cl)有显著性影响,每岁降低1.25％;长期多剂量服用茶碱的哮喘患者,Cl降低26.8％;OLD时Cl降低33.9％;合并用Ac-SPM时Cl略有降低,但影响不大;性别和体重对Cl无显著影响。

Evaluation of theophylline population phar- macokinetics in adult hospitalized patients using NONMEM analysis

The population pharma-cokinetics of theophylline was evaluated using 374 theophylline serum concentration measurements from 72 hospitalized patients through NONMEM analysis. An one-compartment open pharmacokinetic model with first-order absorption and first-order elimination was used. The effects of a variety of factors on Cl and Vd were investigated. Hypothesis testing to evaluated potentially significant factors produced a final regression model. There were about 1. 25 % per year decrease in Cl at the age of 18 - 77. Ci was reduced by 26. 8 % for patients with long history of theophylline administration and multiple dosings, and reduced by 33.9 % in OLD patients. Sex, body weight, and coadminis-tration of acetylspiramycin had no significant effects on Cl. Vd was proportional to body weight. The final regression model allowed a priori estimate of the theophylline pharmacokinetic parameters in the patients. These results may be helpful to a rational individualized theophylline dosage regimen.