Determination of Appropriate Weight-Based Cutoffs for Empiric Cefazolin Dosing Using Data from a Phase 1 Pharmacokinetics and Safety Study of Cefazolin Administered for Surgical Prophylaxis in Pediatric Patients Aged 10 to 12 Years

Abstract

ABSTRACT Despite over 40 years of worldwide usage, relatively few data have been published on the pharmacokinetics of cefazolin in pediatric surgical patients. The primary objectives of this study were to examine the pharmacokinetics and safety of cefazolin in children 10 to 12 years of age (inclusive) receiving 1 or 2 g of cefazolin, based on body weight. This multiple-center, open-label study enrolled pediatric patients electively scheduled for surgical procedures who required cefazolin as part of their routine clinical management. Patients weighing ≥25 to <50 kg received a 1-g dose, and patients weighing ≥50 to ≤85 kg received a 2-g dose. Postdose pharmacokinetic and safety assessments were conducted following drug administration. Cefazolin concentration-time data were analyzed by using both noncompartmental and population pharmacokinetics methods. Monte Carlo simulations were performed to identify appropriate weight-based cutoffs for the dosing of children aged 10 to 17 years of age. Twelve patients were enrolled in this study and provided the requisite pharmacokinetic data. In general, cefazolin was well tolerated. The mean cefazolin terminal elimination half-life, clearance, and area under the concentration-time curve from time zero to infinity in this population were 1.95 h, 0.804 ml/min/kg, and 607 mg · h/liter, respectively. Patients weighing 50 to 60 kg exhibited elevated cefazolin exposures. Observed pharmacokinetic parameters and simulation results indicated that a weight-based cutoff of 60 kg is predicted to provide cefazolin exposure consistent with that observed in normal, healthy adults at recommended doses for surgical prophylaxis. (This study has been registered at ClinicalTrials.gov under registration no. NCT01904357.)