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.
Yuen
G J
GJ
School of Pharmacy, Department of Clinical Pharmacy, University of Maryland Baltimore 21201.
Drusano
G L
GL
Brooks
J
J
Flor
S
S
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008297:Male; D008954:Models, Biological; D015242:Ofloxacin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013607:Tablets
D013607:Tablets; D015242:Ofloxacin