Li Z, Chen G
Department of Clinical Pharmacology, Jingling Hospital, Nanjing, China.
Zhongguo Yao Li Xue Bao. 1994 May;15(3):267-70.
The population pharmacokinetics 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. Cl 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 coadministration 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.
通过NONMEM分析,利用72例住院患者的374次茶碱血清浓度测量值评估了茶碱的群体药代动力学。采用具有一级吸收和一级消除的单室开放药代动力学模型。研究了多种因素对清除率(Cl)和分布容积(Vd)的影响。通过假设检验评估潜在的显著因素,得出了最终的回归模型。在18至77岁年龄段,Cl每年约下降1.25%。长期使用茶碱且多次给药的患者Cl降低了26.8%,老年患者降低了33.9%。性别、体重以及与乙酰螺旋霉素合用对Cl无显著影响。Vd与体重成正比。最终的回归模型能够对患者的茶碱药代动力学参数进行先验估计。这些结果可能有助于制定合理的个体化茶碱给药方案。