Yuen G J, Drusano G L, Brooks J, Flor S
School of Pharmacy, Department of Clinical Pharmacy, University of Maryland Baltimore 21201.
Pharmacotherapy. 1992;12(2):88-92.
To compare the effect of age on pharmacokinetics of orally administered ofloxacin, two separate studies were reanalyzed using mixed-effect modeling with the program NONMEM. Subjects were male volunteers, 36 age 65 years or greater and 24 age 18-40 years. The younger group received three 100-mg tablets and the older group received two 200-mg tablets of ofloxacin. Serial blood samples obtained throughout dosing were assayed for drug concentrations using high-performance liquid chromatography. A pharmacostatistical model was developed for the data using mixed-effect modeling with NONMEM. A one-compartment open model with first-order absorption, which included the covariables weight and age, best fit the data. Mean (SE) population values were clearance/F 0.219 (0.009) L/hr/kg, volume of distribution/F 1.50 (0.071) L/kg, and absorption rate constant 2.26 (0.048) hr-1. Older subjects had a 29% lower clearance and 13% lower volume of distribution then the younger subjects.
为比较年龄对口服氧氟沙星药代动力学的影响，使用NONMEM程序通过混合效应模型对两项独立研究进行了重新分析。研究对象为男性志愿者，36名年龄在65岁及以上，24名年龄在18 - 40岁。较年轻组服用三片100毫克的氧氟沙星片剂，较年长组服用两片200毫克的氧氟沙星片剂。在整个给药过程中采集的系列血样使用高效液相色谱法测定药物浓度。使用NONMEM通过混合效应模型为数据建立了药物统计学模型。一个具有一级吸收的单室开放模型，其中包括协变量体重和年龄，最符合数据。平均（标准误）总体参数值为清除率/F 0.219（0.009）升/小时/千克，分布容积/F 1.50（0.071）升/千克，吸收速率常数2.26（0.048）小时⁻¹。年长受试者的清除率比年轻受试者低29%，分布容积低13%。
