Pharmacokinetic considerations in treating invasive pediatric fungal infections

ABSTRACT

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

KEYWORDS:

• Echinocandins
• imidazoles
• invasive mycoses
• triazoles
• nucleoside analogues
• ontogeny
• polyenes
• therapeutic drug monitoring

Article highlights

• Though the influence of normal growth and development in the pediatric patient significantly influences the pharmacokinetics of several antifungals, these observations cannot be universally applied across all drugs in a given class.

• Antifungal formulation, and the recommendations made regarding their administration in relation to food and concomitant medications, is critically important when managing invasive fungal infections.

• Given the wide degree of inter-individual variability observed in the pharmacokinetic behavior of most antifungals, these drugs are poised for therapeutic drug monitoring. However, current applications are limited and would be markedly enhanced with the availability of more robust pharmacodynamic data. Additionally, guidance on dosing adjustments, frequency of drug monitoring, sampling strategies, and outcomes associated with drug monitoring are still urgently needed, especially among the pediatric population.

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Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.