Integrating anatomo‐physiological changes and pharmacogenomics in anti‐infective therapy management: is it a major concern?

Beaumier, Laura; Chanoine, Sébastien; Gautier-Veyret, Élodie; Pluchart, Hélène; Cornet, Muriel; Brenier-Pinchart, Marie-Pierre; Fonrose, Xavier; Camara, B.; Bedouch, Pierrick

doi:10.1111/bcp.13785

Cited by 1 publication

(1 citation statement)

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“…144 Attention should be paid to cachexia in cancer patients, who are at risk of low levels of CYP3A4 activity due to possible interleukin genetic mutation 145 and VRZ underexposure due to anatomical and physiological changes, including mucosal atrophy. 146…”

Section: Coexisting Factors Obesity Bariatric Surgerymentioning

confidence: 99%

Antifungal Drugs TDM: Trends and Update

Kably

Launay

Derobertmasure

et al. 2022

Therapeutic Drug Monitoring

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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.

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Section: Coexisting Factors Obesity Bariatric Surgerymentioning

confidence: 99%