Variability of ciprofloxacin pharmacokinetics in children: impact on dose range in sickle cell patients. (6th September 2018)

• Record Type: Journal Article
• Authors: Facchin, A; Bui, S; Leroux, S; Nacka, F; Koehl, B; Maksoud, E; Fayon, M; Jacqz-Aigrain, E
• Is Part Of: Journal of antimicrobial chemotherapy. Volume 73:Number 12(2018)
• Page Start: 3423
• Page End: 3429
• Publication Date: 2018-09-06
• Subjects: Anti-infective agents -- Periodicals; Chemotherapy -- Periodicals; 615.58
• DOI: 10.1093/jac/dky328
• Languages: English
• ISSNs: 0305-7453

Abstract

Abstract: Objectives: To determine the ciprofloxacin population pharmacokinetics in paediatric patients and the impact of underlying disease and evaluate the appropriateness of current dosage regimens. Patients and methods: Plasma concentrations of ciprofloxacin from children treated with ciprofloxacin were measured by HPLC. The pharmacokinetic population analysis was performed using NONMEM v7.2 (Icon Development Solutions, USA). Results: Two datasets were combined and 128 plasma concentrations in 60 patients aged 5.6 years (range 0.3–18.9), treated with a median daily dose of 30.0 mg/kg (range 6.5–52.0) presenting with sickle cell disease (SCD; n = 20, 33%), haemopathy ( n = 15, 25%), cystic fibrosis (CF; n = 3, 5%) and other diseases ( n = 22, 37%) were analysed. Data were best described by a two-compartment model with first-order elimination. Ciprofloxacin clearance (mean ± SD) was 0.81 ± 0.30 L/h/kg, increased allometrically with weight, decreased with increasing creatinine concentration, was 89% higher in SCD compared with non-SCD patients and increased by 0.95 L/h/kg per year of age. The volume of distribution was 6.9 L/kg and depended only on the weight. Monte Carlo simulations were performed separately in SCD and non-SCD patients to target an AUC/MIC ratio >125 at steady-state, required for antibacterial efficacy, and recommendations of dosing regimens were proposed. Conclusions: In addition to known covariates, ciprofloxacin clearance is greater in SCD children compared with non-SCD patients. The dosing of this agent needs to be adapted to this subgroup of patients.