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 volunt eers and uninfected patients) included in 10 pharmacokinetic studies o f fleroxacin after oral administration, The objectives of this analysi s were (i) to estimate the typical values of two hey pharmacokinetic p arameters, clearance over systemic availability (CL/F) and volume of d istribution over systemic availability (V/F), after the administration of therapeutic doses and (ii) to study qualitatively and quantitative ly the factors which influence the elimination and distribution of fle roxacin, The main pharmacokinetic parameters, CL/F and V/F, were analy zed separately by a standard two-stage approach, The covariates invest igated were predicted creatinine clearance (CL,,), age, gender, body s urface 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 typica l male subject (CL(CR), 70 ml/min; LBW, 54 kg; age, 54 years), Modelin g of CL/F indicated that this parameter increases linearly with CL(CR) , decreases linearly with age, and is 10.8 ml/min lower in females tha n in males, The best model for V/F showed a linear increase with LBW a nd 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 CL(CR), age, and gender influence the elimination of fleroxacin f rom the body, whereas V/F is influenced by LBW, age, and gender.