Anti-infectives in Pediatric Patients with Cystic Fibrosis: A Comprehensive Review of Population Pharmacokinetic Analyses

Pulmonary complications are the leading cause of morbidity and mortality in pediatric patients with cystic fibrosis. Altered pharmacokinetic parameters in this population, as well as high inter- and intra-individual variability, complicate the optimization of anti-infective treatments. In this review, we aim to summarize and describe all anti-infective population pharmacokinetic (popPK) models applied to pediatric populations with cystic fibrosis. Our objectives were to identify the most-reported structural models and retained covariates and to compare the dosing regimens used in clinical routine with those recommended in literature and guidelines. A literature search was done through the PubMed database from inception to August 2024. Studies were retained only if they complied with the inclusion and exclusion criteria. The review included 21 popPK models covering the pharmacokinetic profiles of eight different molecules. Among these, five are recommended antibiotics for treating pulmonary infections in patients with cystic fibrosis. All models incorporated body composition and/or renal function measures as covariates in their pharmacokinetic parameter equations. Standard dosing regimens in the studies were consistent with guidelines and literature recommendations. This is the first review summarizing and describing all anti-infective popPK models in pediatric patients with cystic fibrosis. Improved estimation of pharmacokinetic parameters and a clearer understanding of variability sources will enhance the optimization of antibiotic treatment in clinical practice. Finally, the impact of new targeted therapies on the management of this population will have to be closely monitored in the years ahead.