Factors influencing elimination and distribution of fleroxacin: metaanalysis of individual data from 10 pharmacokinetic studies.
A metaanalysis was conducted on data from 172 subjects (healthy volunteers and uninfected patients) included in 10 pharmacokinetic studies of fleroxacin after oral administration. The objectives of this analysis were (i) to estimate the typical values of two key pharmacokinetic parameters, clearance over systemic availability (CL/F) and volume of distribution over systemic availability (V/F), after the administration of therapeutic doses and (ii) to study qualitatively and quantitatively the factors which influence the elimination and distribution of fleroxacin. The main pharmacokinetic parameters, CL/F and V/F, were analyzed separately by a standard two-stage approach. The covariates investigated were predicted creatinine clearance (CLCR), age, gender, body surface area, body weight, and lean body weight (LBW). The predicted CL/F and V/F were 83.5 ml/min and 101 liters, respectively, for a typical male subject (CLCR, 70 ml/min; LBW, 54 kg; age, 54 years). Modeling of CL/F indicated that this parameter increases linearly with CLCR, decreases linearly with age, and is 10.8 ml/min lower in females than in males. The best model for V/F showed a linear increase with LBW and a linear decrease with age. V/F was found to be 20.4 liters greater in males than in females. In conclusion, this metaanalysis has shown that CLCR, age, and gender influence the elimination of fleroxacin from the body, whereas V/F is influenced by LBW, age, and gender.
Reigner
B G
BG
Department of Clinical Pharmacology, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Welker
H A
HA
D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000493:pharmacokinetics*; D001682:Biological Availability; D003404:Creatinine / Q000378:metabolism; D005260:Female; D016576:Fleroxacin / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D015999:Multivariate Analysis; D012044:Regression Analysis; D012189:Retrospective Studies; D012727:Sex Characteristics
D000890:Anti-Infective Agents; D003404:Creatinine; D016576:Fleroxacin