Therapeutic Drug Monitoring of Antifungals: Pharmacokinetic and Pharmacodynamic Considerations
Jeannina A. Smith, David R. Andes
Abstract
Jeannina A. Smith, David R. Andes
Abstract
Therapeutic drug monitoring of any pharmacologic agent should be considered when there is both significant pharmacokinetic variability and strong, clinically relevant, exposure-effect relationships. Many antifungal drugs exhibit marked variability in drug concentration as a result of inconsistent absorption, metabolism, elimination, or interaction with concomitant medications. For each of the available antifungal drugs, both preclinical and clinical trials have exhibited a relationship between serum concentrations and treatment efficacy. For a smaller subset of compounds, a similar relationship has been identified for the toxicity. The kinetic variability among patients falls outside the therapeutic window for a group of four antifungal compounds. This review summarizes the current literature on therapeutic drug monitoring for these antifungal agents.
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Therapeutic drug monitoring of any pharmacologic agent should be considered when there is both significant pharmacokinetic variability and strong, clinically relevant, exposure-effect relationships. Many antifungal drugs exhibit marked variability in drug concentration as a result of inconsistent absorption, metabolism, elimination, or interaction with concomitant medications. For each of the available antifungal drugs, both preclinical and clinical trials have exhibited a relationship between serum concentrations and treatment efficacy. For a smaller subset of compounds, a similar relationship has been identified for the toxicity. The kinetic variability among patients falls outside the therapeutic window for a group of four antifungal compounds. This review summarizes the current literature on therapeutic drug monitoring for these antifungal agents.
Key concepts: Pharmacokinetics, Therapeutic drug monitoring, Pharmacology, Drug, Pharmacodynamics, Antifungal drugs, Medicine, Antifungal