Pharmacokinetics of ciprofloxacin in children with complicated urinary tract infection: results of a multicenter population pharmacokinetic study. [PublishAheadOfPrint]

Resistance rates for ciprofloxacin, which is labeled for treating complicated urinary tract infections in children, are rapidly rising. As there is limited knowledge on developmental pharmacology of ciprofloxacin, the primary aim of this study was to develop a population pharmacokinetic model for ciprofloxacin in children treated for complicated urinary tract infections. Children to whom ciprofloxacin was prescribed, intravenous (10-15 mg/kg body weight every 12 h) or per os (15-20 mg/kg every 12 h), were enrolled. 108 Serum and 119 urine samples were obtained during 10 intravenous and 13 oral courses of ciprofloxacin in 22 patients (age range 0.31 – 15.51 years). A one-compartment model best described our data. Fat free mass and glomerular filtration rate (estimated by a formula using cystatin C and creatinine), standardized for body surface area, were significant covariates for ciprofloxacin clearance. In our population, ciprofloxacin clearance is 0.16 – 0.43 L/h/kg of body weight, volume of distribution 0.06 – 2.88 L/kg, and bioavailability 59.6%. All of our patients had a clinical cure of their infection. Based on target attainment simulations across doses, all children reached the pharmacodynamic target for Enterobacteriaceae, but on average only 53% for Pseudomonas aeruginosa, and 3% for Staphylococcus aureus, at the 15 mg/kg oral dose. For treating urinary tract infections caused by Pseudomonas aeruginosa, oral doses should be at least 20 mg/kg. Furthermore, in our population, fat free mass and kidney function should be considered as they prove to be significant covariates for ciprofloxacin clearance and hence, exposure.

https://ift.tt/2m6sPfP