Population pharmacokinetics of amikacin in patients with pediatric cystic fibrosis

Abstract

Introduction Amikacin is commonly used in patients with pediatric cystic fibrosis (CF) for the treatment of pulmonary exacerbations. Amikacin efficacy is related to maximum plasma concentration/minimum inhibitory concentration (Cmax/MIC) ratio >8. Pharmacokinetic data in patients with pediatric CF are scarce. The aim of this study was to develop a population pharmacokinetic (PopPK) model describing amikacin disposition in patients with pediatric CF. Methods CF patients under 18 years of age with pulmonary exacerbation who received amikacin were enrolled. Patients received different amikacin regimens (30 mg−1 kg−1 day−1 every 8, 12, or 24 hours) depending on the patient's status and hospital protocols. Amikacin serum levels were obtained for therapeutic drug monitoring. PopPK model was developed using MONOLIX Suite‐2018R1 (Lixoft). Results A total of 39 patients (114 amikacin concentrations) were included in this study. Population estimates for the elimination rate constant (k) and the volume of distribution (V) were 0.541 hours−1 and 0.451 L/kg, respectively. Between‐subject and between‐occasion variability were 53% and 16.5% for k and 31% and 22% for V, respectively. Bodyweight was a significant covariate associated with V. Based on simulations, almost 70% of the patients receiving 30 mg−1 kg−1 day−1 every 24 hours would achieve a Cmax/MIC ratio >8 which is an appropriate therapeutic goal while no patient in the other two groups (Q8 and Q12) would achieve that objective. Conclusions The regimen of 30 mg−1 kg−1 day−1 every 24 hours more adequately fulfilled the therapeutic target for amikacin. Although all our patients had good clinical results and a good adverse‐events profile, further studies are necessary to redefine the optimal treatment strategy.

Evaluating the efficacy of inhaled amikacin as an adjunct to intravenous combination therapy (ceftazidime and amikacin) in pediatric cystic fibrosis pulmonary exacerbation

“…It is perceived that the pharmacokinetics of antibiotics in the CF patients differ from others. It is essential to conduct pharmacokinetic studies to maximize clinical effects, select optimal treatment regimens, and minimize the side effects of antibiotics ( Caceres Guido et al, 2019 ). When using Amikacin, ototoxicity and renal toxicity are possible side effects ( Mulheran et al, 2001 ; Young et al, 2013 ).…”

evaluación de desempeño del servicio de dosificación de precisión para vancomicina en un hospital pediátrico de nivel terciario

“…y publicaciones de investigaciones (siempre asociadas a temas de farmacocinética y farmacología clínica, aunque no solo de antibióticos), observamos un incremento sostenido a lo largo del período evaluado (cantidad media de presentaciones por año, por período: 4 en 2007-2010 vs 7 en 2011-2020). En este sentido, el cambio más relevante se produjo en relación a la importancia, medida en términos del factor de impacto de las revistas en la que fueron publicados estos trabajos, correspondiendo los de la última etapa a revistas de mayor factor de impacto en relación al primer período 26-29 . Asimismo, las actividades de formación de recursos humanos en ámbitos profesionales, incluyendo a universidades, sociedades científicas y demás instituciones de similar envergadura, también mostraron un incremento constante (cantidad media de actividades docentes por año, por período: 5 en 2007-2010 vs 11 en 2011-2020).…”

Therapeutic drug monitoring in developing nations: assessing the current state of affairs in South America

“…Dr. Suarez-Kurtz also coordinates the Brazilian Pharmacogenetics Network, an initiative of Brazilian researchers, which aims to promote and coordinate integrated research projects in pharmacogenetics/pharmacogenomics in the Brazilian population (REFARGEN). Still, interesting studies on TDM in children were performed in Argentina, a population evaluation of pharmacokinetics of amikacin in patients with cystic fibrosis [7], and in Chile, an evaluation of drug interaction of voriconazole and cyclosporine in hematopoietic stem cell transplantation [8].…”