Journal
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
Volume 84, Issue 11, Pages 2544-2550Publisher
WILEY
DOI: 10.1111/bcp.13707
Keywords
clinical pharmacology; drug interactions; infectious diseases; pharmacokinetics; therapeutic drug monitoring; transplantation
Categories
Funding
- F2G
- AiCuris
- Astellas Pharma
- Spero Therapeutics
- Matinas Biosciences
- Antabio
- Amplyx
- Allecra
- Auspherix
- Pfizer
- National Institutes of Health
- Medical Research Council
- National Institute of Health Research
- FDA
- European Commission (FP7)
- European Commission (IMI)
- Basilea Pharmaceutica
- Gilead Sciences
- Merck Sharp Dohme
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AimsThe aim of this study was to determine clinical variables associated with posaconazole exposure among adult patients with haematological malignancies who received posaconazole tablets for prophylaxis of invasive fungal infections (IFIs). MethodsThe study population included adult patients with haematological malignancies who received posaconazole delayed-release tablets for prophylaxis of IFIs after induction chemotherapy for acute leukaemia or graft-versus-host-disease (GVHD) complicating hematopoietic stem cell transplantation (HSCT) in the period January 2016-December 2017. ResultsSixty-six consecutive patients with 176 posaconazole C-min were included for evaluation in the study. Subtherapeutic posaconazole concentrations (< 0.7mgl(-1)) were observed at least once in 33.3% of patients (22/66), and overall in 17.0% of therapeutic drug monitoring (TDM) episodes (30/176). At multilevel linear regression, use of PPIs (P=0.008), use of intermediate or high dose steroids (>0.7mgkg(-1) daily) (P=0.022) and male gender (P=0.025) were significantly associated with decreased C-min, whereas time from starting therapy (P=0.032) was associated with increased C-min in our patient population. ConclusionPosaconazole exposure during treatment with delayed-released tablet formulation may be affected by the use of PPIs and/or of intermediate or high dose steroids.
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