Pharmacokinetic considerations in treating invasive pediatric fungal infections.
BACKGROUND
Despite the increased availability of systemic antifungal agents in recent years, the management of invasive fungal disease is still associated with significant morbidity and mortality. Knowledge of a drug's pharmacokinetic behavior is critical for optimizing existing treatment strategies.


METHODS
This review examines the pharmacokinetics of the major drug classes used to treat invasive mycoses including the echinocandins, imidazoles, triazoles, nucleoside analogs, and polyenes. It examines the mechanisms behind dose-exposure profiles that differ in children as compared with adults and explores the utility of pharmacogenetic testing and therapeutic drug monitoring.


CONCLUSIONS
Lifesaving medical advances for oncologic and autoimmune conditions have resulted in a significant increase in the frequency of opportunistic fungal infections. Owing to the high rate of treatment failures observed when managing invasive fungal infections, strategies to optimize antifungal therapy are critical when caring for these complex patients. Opportunities to maximize positive outcomes include dose refinement based on age or genetic status, formulation selection, co-administration of interacting medications, and administration with regard to food. The application of therapeutic drug monitoring for dose individualization is a valuable strategy to achieve pharmacodynamic targets.
a Department of Pediatrics , UMKC School of Medicine , Kansas City , MO , USA.|b Drug Safety Service Children's Mercy Hospital , Kansas City , MO , USA.|c Antimicrobial Stewardship Program Children's Mercy Hospital , Kansas City , MO , USA.|d Divisions Pediatric Infectious Diseases & Clinical Pharmacology , Toxicology, and Therapeutic Innovation Children's Mercy Hospital , Kansas City , MO , USA.
Jennifer L
JL
Goldman
a Department of Pediatrics , UMKC School of Medicine , Kansas City , MO , USA.|d Divisions Pediatric Infectious Diseases & Clinical Pharmacology , Toxicology, and Therapeutic Innovation Children's Mercy Hospital , Kansas City , MO , USA.
Susan M
SM
Abdel-Rahman
D000328:Adult; D000367:Age Factors; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000145:classification / Q000493:pharmacokinetics; D002648:Child; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D000072742:Invasive Fungal Infections / Q000188:drug therapy*; D009894:Opportunistic Infections / Q000188:drug therapy / Q000382:microbiology; D010597:Pharmacogenetics / Q000379:methods
D000935:Antifungal Agents
Echinocandins; imidazoles; invasive mycoses; nucleoside analogues; ontogeny; polyenes; therapeutic drug monitoring; triazoles