Antifungal Drugs TDM: Trends and Update

Abstract

The increasing burden of invasive fungal infections results in growing challenges to antifungal (AF) therapeutic drug monitoring (TDM). This review aims to provide an overview of recent advances in AF TDM. Methods:We conducted a PubMed search for articles during 2016-2020 using "TDM" or "pharmacokinetics" or "drug-druginteraction" with "antifungal," consolidated for each AF. Selection was limited to English language articles with human data on drug exposure.Results: More than 1000 articles matched the search terms. We selected 566 publications. The latest findings tend to confirm previous observations in real-life clinical settings. The pharmacokinetic variability related to special populations is not specific but must be considered. AF benefit-to-risk ratio, drug-drug interaction (DDI) profiles, and minimal inhibitory concentrations for pathogens must be known to manage at-risk situations and patients. Itraconazole has replaced ketoconazole in healthy volunteers DDI studies. Physiologically based pharmacokinetic modeling is widely used to assess metabolic azole DDI. AF prophylactic use was studied more for Aspergillus spp. and Mucorales in oncohematology and solid organ transplantation than for Candida (already studied). Emergence of central nervous system infection and severe infections in immunocompetent individuals both merit special attention. TDM is more challenging for azoles than amphotericin B and echinocandins. Fewer TDM requirements exist for fluconazole and isavuconazole (ISZ); however, ISZ is frequently used in clinical situations in which TDM is recommended. Voriconazole remains the most challenging of the AF, with toxicity limiting high-dose treatments. Moreover, alternative treatments (posaconazole tablets, ISZ) are now available.Conclusions: TDM seems to be crucial for curative and/or longterm maintenance treatment in highly variable patients. TDM poses fewer cost issues than the drugs themselves or subsequent treatment issues. The integration of clinical pharmacology into multidisciplinary management is now increasingly seen as a part of patient care.

Effect of Therapeutic Plasma Exchange on Itraconazole Pharmacokinetics: A Case Study

“…Concerningly, this value exceeds both the therapeutic range (0.5-1 mg/L) and toxicity threshold ($3 mg/L) for trough itraconazole concentrations. 12 In this case, however, the patient did not experience any adverse outcomes attributable to supratherapeutic plasma concentrations of itraconazole.…”

Antifungal Activity of Nontoxic Nanocomposite Based on Silver and Reduced Graphene Oxide against Dermatophytes and Candida spp

“…Additionally, the oral route is often used for fluconazole, so the prolonged treatment time causes hepatotoxic damage and cytotoxic activity on human leukocytes. 65,76 The in vivo toxicity assays in G. mellonella have several an advantages over traditional mammalian models. They can be easilyand economically obtained on a large scale, with a life cycle of 7 to8 weeks).…”

Aspergillosis: an Update on Clinical Spectrum, Diagnostic Schemes, and Management

“…Voriconazole and posaconazole are CYP3A4 inhibitors, and drug interactions are possible when coupled with drugs metabolized by this same pathway. Therapeutic drug monitoring (TDM) is recommended for individuals who receive a long course of azoles, as it helps to maximize therapeutic efficacy and drug toxicity and detect suboptimal drug levels [ 70 ]. TDM is recommended for itraconazole, voriconazole, and posaconazole.…”