ESPN 51th Annual Meeting

ESPN 2018


 
High doses of oral ciprofloxacin are required for treating Pseudomonas aeruginosa pyelonephritis, results of a population pharmacokinentic study
KEVIN MEESTERS 1 ROBIN MICHELET 2 ANN RAES 1 JOHAN VANDE WALLE 1

1- DEPARTMENT OF PEDIATRIC NEPHROLOGY, GHENT UNIVERSITY HOSPITAL
2- FACULTY OF PHARMACEUTICAL SCIENCES, LABORATORY OF MEDICAL BIOCHEMISTRY AND CLINICAL ANALYSIS, GHENT UNIVERSITY
 
Introduction:

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.

Material and methods:

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. Different serum and urine samples were obtained after administration. Ciprofloxacin concentrations were measured using a  high-performance liquid chromatographic HPLC method. A population pharmacokinetic model was developed using the NONNEM software. Different covariates were included.

Results:

A total of 108 serum and 119 urine samples were obtained from 22 children. 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, at the 15 mg/kg oral dose.

Conclusions:

For treating urinary tract infections caused by Pseudomonas aeruginosa, oral doses should be at least 20 mg/kg every 12 h. Furthermore, in our population, fat free mass and kidney function should be considered as covariates for ciprofloxacin clearance and hence, drug exposure.