Therapeutic drug monitoring (TDM) of antifungal agents: guidelines from the British Society for Medical Mycology

Abstract

The burden of human disease related to medically important fungal pathogens is substantial. An improved understanding of antifungal pharmacology and antifungal pharmacokinetics-pharmacodynamics has resulted in therapeutic drug monitoring (TDM) becoming a valuable adjunct to the routine administration of some antifungal agents. TDM may increase the probability of a successful outcome, prevent drug-related toxicity and potentially prevent the emergence of antifungal drug resistance. Much of the evidence that supports TDM is circumstantial. This document reviews the available literature and provides a series of recommendations for TDM of antifungal agents.

Pharmacodynamics of Amphotericin B Deoxycholate, Amphotericin B Lipid Complex, and Liposomal Amphotericin B against Aspergillus fumigatus

“…Deciding which patients have concentration-dependent ther- apeutic failure at the bedside is problematic-therapeutic drug monitoring is not generally advocated for amphotericin B (26), and there are no widely accepted drug exposure targets that can be used to direct dosage adjustment. Both laboratory and clinical studies have demonstrated that serum galactomannan is a prognostic marker of the therapeutic response in IPA (27)(28)(29).…”

Determination of Posaconazole in Plasma/Serum by High-Performance Liquid Chromatography with Fluorescence Detection

“…Therapeutic drug monitoring of a patient's serum or plasma has been a useful tool to detect drug exposures outside of the therapeutic window and to help individualize a dosage regimen and treatment, increasing therapeutic efficacy, and decreasing side effects . Reported methods for the analysis of posaconazole are mostly high-performance liquid chromatography (HPLC) with mass spectrometry [13][14][15][16][17][18][19][20][21][22][23][24][25], ultraviolet [26][27][28][29][30][31] and fluorescence [32][33][34][35] detections. Mass spectrometry (MS) and tandem mass spectrometry (MS/MS) are superior in sensitivity and specificity to ultraviolet (UV) and fluorescence (FL) detections.…”

Therapeutic drug monitoring of voriconazole: validation of a novel ARK™ immunoassay and comparison with ultra-high performance liquid chromatography

“…However, in patients, oral bioavailability might be much lower, as these patients are frequently suffering from gastro-intestinal complications [6,7]. Other factors that contribute to the variability in VRC plasma concentrations are the Michaelis-Menten (non-linear) pharmacokinetics of VRC, polymorphisms of the gene encoding the CYP2C19 enzyme, drug-drug interactions, liver disease and age [4]. The large variability in VRC plasma concentrations together with the narrow therapeutic window for treating patients with IFIs, makes individualized dosing adjustments based on therapeutic drug monitoring (TDM) of VRC necessary to optimize therapeutic response and to minimize the probability of neurotoxicity [6].…”

“…The large variability in VRC plasma concentrations together with the narrow therapeutic window for treating patients with IFIs, makes individualized dosing adjustments based on therapeutic drug monitoring (TDM) of VRC necessary to optimize therapeutic response and to minimize the probability of neurotoxicity [6]. According to the BSMM, VRC plasma concentrations should be measured in the first 5 days of therapy and regularly thereafter [4].…”