摘要
目的考察肾移植患者口服普乐可复(FK506)胶囊常规监测群体药代动力学特征,为临床调整个体化给药方案提供依据。方法回顾性收集我院88例肾移植患者的366个FK506全血稳态浓度样本,建立FK506群体分析数据库,用非线性混合效应模型法进行模型优化,确定FK506的药代动力学模型和统计学模型。分别考察性别、年龄、体重、术后时间等因素对药代动力学参数的影响,得到模型方程并进行个体化给药方案设计。结果FK506数据用稳态药代动力学模型进行描述,通过模型优化表明,剂量、肌酐和尿素氮对药代动力学参数有显著性影响。结论本方法可用于临床调整给药方案。
Objective To evaluate the population pharmacokinetic character of orally tacrolimus(FK506) from routine drug monitoring data after renal transplantation and to provide the evidence of the schedule of individual dosage. Methods Routine monitoring FK506 whole blood concentration data were collected retrospectively and estimated by nonlinear mixed effect model(NONMEM) program. There were 88 patients and 366 concentration data and built the FK506 population database. The fixed effect factors, such as gender, age, weight ,period after operation, and so on. The individual dosage schedule was also designed using the population pharmacokinetic results. Results The steady-state model was fitted in the routine monitoring drug concentration and the POSTHOC sub-program was used to calculate the data model. The statistic analysis indicated that the dosage, creatinine and blood urea nitrogen had apparent influence on the result. Conclusion The veracity of the model was good and an good fitness was derived from the population model that should provide a new approach for cli- nical adjustment of the oral FK506 dosage.
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2005年第3期205-208,共4页
The Chinese Journal of Clinical Pharmacology
基金
国家高技术研究发展(863)计划资助项目(2003AA2Z3413)
关键词
群体药代动力学
普乐可复
非线性混合效应模型
个体化给药
population pharmacokinetics
tacrolimus
nonlinear mixed effect model
individual drug dosage design$$$$
