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Voriconazole therapeutic drug monitoring – interindividual variability and pharmacokinetic modelling (poster)

Název česky Terapeutické monitorování vorikonazolu - interindividuální variabilita a farmakokinetické modely


Rok publikování 2022
Druh Další prezentace na konferencích
Popis Interpretation of TDM is one of the main activities of clinical pharmacists. One of the classes of drugs recommended for TDM is anti-infectives; recently, among them second-generation triazoles. TDM of voriconazole should be performed for most patients due to interindividual variability in pharmacokinetics. Precise pharmacokinetic models are highly useful in clinical settings for such a routine TDM. Our study aims to assess the interindividual variability in pharmacokinetics of voriconazole and to evaluate the reliability of the available pharmacokinetic model. A retrospective observational cohort study in 19 adult patients treated with voriconazole. Data collected: measured plasma levels, descriptive patient data, and information on concomitant medications. A comparison between voriconazole levels predicted by the pharmacokinetic model (MWPharm Online, Mediware a.s., version and the measured levels was performed. In addition, a case study of a patient with cystic fibrosis and TDM as an optimization treatment strategy is presented. From all the voriconazole levels measured at a steady-state (n=43) only 60% are within the target therapeutic range for voriconazole treatment (1 – 5,5 mg/l), 33% are subtherapeutic and 7% are supratherapeutic. When a minimal target through concentration is considered 2 mg/l, as newly recommended, nearly one-half of measurements are subtherapeutic. The mean difference between predicted and measured voriconazole levels is 2,3 mg/l (SD=2,01); minimal and maximal differences 0,05 and 7,02 mg/l respectively. Approximately half of the predictions are lower than measured levels. Genetic polymorphism, drug interactions (specifically PPIs were often co-administrated), and elimination organs functions may have an impact on the observed variability. Moreover, the effect of population characteristics, the model vs. the study population, is considered an important factor. The case study demonstrates the clinical benefit of voriconazole TDM in individualized treatment. Preliminary data indicate the need for precise and subpopulation-specific pharmacokinetic models for higher clinical utility of voriconazole TDM. These data support the importance of routine TDM of voriconazole.

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