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Use of Nonlinear, Mixed‐Effects Modeling for Population Analysis of Ofloxacin: Effects of Age on Oral Drug Pharmacokinetics
Author(s) -
Yuen Geoffrey J.,
Drusano George L.,
Brooks Janet,
Flor Soledad
Publication year - 1992
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/j.1875-9114.1992.tb03614.x
Subject(s) - nonmem , ofloxacin , pharmacokinetics , volume of distribution , medicine , population , dosing , elimination rate constant , population pharmacokinetics , oral administration , pharmacology , chemistry , antibiotics , biochemistry , environmental health , ciprofloxacin
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.