Use of nonlinear, mixed-effects modeling for population analysis of ofloxacin: effects of age on oral drug pharmacokinetics.

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.