Population pharmacokinetics of ciprofloxacin in pediatric and adolescent patients with acute infections.
The aim of the present study was to characterize the population pharmacokinetics of ciprofloxacin in patients with and without cystic fibrosis ranging in age from 1 day to 24 years and to propose a limited sampling strategy to estimate individual pharmacokinetic parameters. Patients were divided into four groups according to the treatment schedule. They received ciprofloxacin by intravenous infusion (30 min) or by the oral route. The number of samples collected from each patient ranged from 1 to 12. The population parameters were computed for an initial group of 37 patients. The data were analyzed by nonlinear mixed-effect modeling by use of a two-compartment structural model. The interindividual variability in clearance (CL) was partially explained by a dependence on age and the patient's clinical status. In addition, a significant relationship was found between weight and the initial volume of distribution. Eighteen additional patients were used for model validation and evaluation of limited sampling strategies. When ciprofloxacin was administered intravenously, sampling at a single point (12 h after the start of infusion) allowed the precise and accurate estimation of CL and the elimination half-life, as well as the ciprofloxacin concentration at the end of the infusion. It should be noted that to take into account the presence of a lag time after oral administration, a schedule based on two sampling times of 1 and 12 h is needed. The results of this study combine relationships between ciprofloxacin pharmacokinetic parameters and patient covariates that may be useful for dose adjustment and a convenient sampling procedure that can be used for further studies.
D000208:Acute Disease; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001499:Bayes Theorem; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D002939:Ciprofloxacin / Q000097:blood / Q000493:pharmacokinetics*; D003198:Computer Simulation; D003550:Cystic Fibrosis / Q000382:microbiology; D006207:Half-Life; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D008954:Models, Biological; D011153:Population; D011552:Pseudomonas Infections / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D012680:Sensitivity and Specificity
D002939:Ciprofloxacin