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Published on: November 8, 2015
Plasma Concentrations of Prophylactic Posaconazole and Risk Factors for Subtherapeutic Exposure in Taiwanese Patients
Hsing-Yu Lin1, Shu-Chen Hu2, Tsung-Yu Pai1
1Department of Pharmacy, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
Background:
Posaconazole is widely used for antifungal prophylaxis in patients with hematologic malignancies. However, interindividual pharmacokinetic variability may lead to subtherapeutic exposure and treatment failure. Real-world data on the pharmacokinetics of posaconazole tablets and infusion in East Asian populations remain limited. This study aims to evaluate the plasma concentration of posaconazole and risk factors for subtherapeutic exposure in Taiwanese patients.
Methods:
This nested case-control study was conducted using data from the National Taiwan University Hospital database. The study cohort comprised adult patients with hematologic malignancies receiving delayed-release tablets or intravenous formulations of posaconazole and undergoing therapeutic drug monitoring. Factors associated with subtherapeutic posaconazole exposure (<0.7 μg/mL) were identified through multivariate logistic regression. Supratherapeutic concentration was defined as a level >1.83 μg/mL.
Results:
Of a total of 221 patients, 24.9% and 24.0% exhibited subtherapeutic and supratherapeutic posaconazole concentrations, respectively. Multivariate logistic regression indicated that male sex (odds ratio [OR] = 2.31), diarrhea (OR = 2.18), and concurrent use of proton pump inhibitors (OR = 2.00) or prokinetic agents (OR = 2.17) were independently associated with subtherapeutic exposure to posaconazole.
Conclusion:
Subtherapeutic and supratherapeutic exposures to posaconazole remain a concern despite standard dosing. Therapeutic drug monitoring and personalized risk assessment are essential for optimizing antifungal prophylaxis in patients with hematologic malignancies.
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