Optimizing antifungal treatment through pharmacometrics: dosing considerations for enhanced efficacy
- L. Chen
- Tuesday 19 December 2023
2311 GJ Leiden
- Prof.dr. C.A.J. Knibbe
- dr. E.H.J. Krekels
- dr. R.J. Brüggemann
Fungal infections pose a significant threat to individuals with compromised immune systems and despite advancements in diagnosis and treatment, they continue to jeopardize patient’s health. Maximizing the effectiveness of existing antifungal drugs is imperative. Among these, fluconazole and posaconazole are commonly prescribed to treat severe and life-threatening fungal infections. In this thesis, among others, we aimed to understand better how well different posaconazole formulations are absorbed. Through computational modeling and simulation, we learned that posaconazole is best taken with food to reduce the risk of inadequate drug absorption and subsequent therapeutic failure. This applies not only to the suspension but also to the tablet, which results in higher and more predictable absorption even though it does not achieve concentrations similar to those upon intravenous administration. Fluconazole was studied in individuals with obesity. Our findings indicate that heavier adult males may require a higher dose to achieve the desired exposure. Consequently, we proposed dosing recommendations for treating obese patients.
In summary, this research, which has come to fruition due to a long-term collaboration between Leiden University and Radboudumc, enhanced our knowledge of factors that reduce exposure to antifungal drugs, which allowed us to provide guidance on how to individualize and optimize antifungal treatment in individual patients.
PhD dissertations by Leiden PhD students are available digitally after the defence through the Leiden Repository, that offers free access to these PhD dissertations. Please note that in some cases a dissertation may be under embargo temporarily and access to its full-text version will only be granted later.
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