TDM of antifungals – PK/PD relationship and the use of pharmacokinetic models

MARKOVÁ, Eliška a Kateřina HORSKÁ. TDM of antifungals – PK/PD relationship and the use of pharmacokinetic models. In Student scientific conference - doctoral students 2023. 2023.

Základní údaje

Originální název

TDM of antifungals – PK/PD relationship and the use of pharmacokinetic models

Autoři

MARKOVÁ, Eliška a Kateřina HORSKÁ

Vydání

Student scientific conference - doctoral students 2023, 2023

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Další údaje

Typ výsledku

Prezentace na konferencích

Utajení

není předmětem státního či obchodního tajemství

Klíčová slova česky

vorikonazol, TDM, terapeutické monitorování léčiv, farmakokinetické modely

Klíčová slova anglicky

voriconazole, TDM, therapeutic drug monitoring, pharmacokinetic models

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Anotace

V originále

Background and Objective: Therapeutic drug monitoring (TDM) is becoming an increasingly important (and common) tool for achieving efficient and safe anti-infective therapy. Based on guidelines, TDM of voriconazole should be performed for most patients. To perform TDM in routine clinical practice and fully use its potential, precise and possibly subpopulation-specific pharmacokinetic models are required. Our study aims to assess the interindividual variability in voriconazole pharmacokinetics, target specific subpopulations of patients, and relevant comorbidities. Correspondingly, we aim to evaluate the reliability of currently available pharmacokinetic models. Setting and Method: A retrospective cohort study in 28 patients treated with voriconazole. Data collected: measured voriconazole plasma levels, descriptive patient data, and basic biochemical parameters. Analysis of the data in the context of the target reference range and comparison between voriconazole plasma levels predictions by the pharmacokinetic model (MWPharm Online, Mediware a.s.) and the measured levels were performed. Results: Based on our experiences and preliminary results, the inter (and even intra-)- individual variability in pharmacokinetics is wide. At steady state, only 62% of voriconazole levels are within the target therapeutic range, 27% are subtherapeutic, and 11% are supratherapeutic (total n=70). When a minimal target through concentration is considered 2 mg/l, as newly recommended, one-half of measurements are subtherapeutic; on-label dosing frequently led to subtherapeutic measured levels. The effect of C-reactive protein and body weight on voriconazole levels, recently discussed in the literature, was also assessed in our study; these variables considerably impact voriconazole levels. Moreover, we evaluate the precision of prediction of an available pharmacokinetic model; the mean difference between predicted and measured levels is 5,23 mg/l (SD=4,17), minimal and maximal differences 0,10 and 19,68 mg/l, respectively. More than half of the predictions are higher than measured levels. Conclusion: Our preliminary data support the urgent need for precise and subpopulation-specific pharmacokinetic models for higher clinical utility of voriconazole TDM. These data clearly demonstrate the importance of routine voriconazole TDM and raise the question of standard dosing recommendation adjustments.