AI Article Synopsis
- Posaconazole is an antifungal medication that helps prevent invasive fungal infections (IFIs) but has inconsistent effectiveness due to variable absorption from its oral suspension formulation.
- A study involving 122 adult patients receiving chemotherapy for AML/MDS measured posaconazole concentrations at various points, finding that lower concentrations were linked to a higher occurrence of IFIs.
- The results suggest that therapeutic drug monitoring (TDM) of posaconazole is important, with specific dosages associated with better outcomes, and factors like food intake can significantly influence drug levels.
Article Abstract
Background: Posaconazole has an important role in the prophylaxis of invasive fungal infections (IFIs), however oral suspension formulation is associated with variable bioavailability. The relationship between posaconazole concentrations achieved with the oral suspension and the IFI occurrence were analyzed along with demographic and clinical covariates (mucositis, diarrhea, liver enzymes, co-medications, and food intake).
Methods: One hundred twenty-two adult patients with AML/MDS undergoing remission induction chemotherapy were enrolled. They received posaconazole as prophylaxis and 557 posaconazole measurements were performed with a validated LC-MS/MS method.
Results: The median (range) posaconazole concentration (ng/ml) on days 2, 3, 7, 14, and 21 was 271 (43-493), 564 (101-1461), 713 (85-2186), 663 (85-1994), and 497 (43-1872), respectively. Thirteen patients (11%) developed proven (1/13), probable (2/13), and possible IFIs (10/13). A significant relationship existed between lower steady-state posaconazole concentrations and a higher breakthrough IFI incidence by binary logistic regression (P=0.0108). Posaconazole value of ≥ 338 ng/ml on day 3 predicted the achievement of ≥ 500 ng/ml at day 7 (sensitivity: 78.5%, specificity: 66.7%, AUC: 0.747). Food intake (P=0.0014) and proton pump inhibitor (P=0.0063) were significantly associated with higher and lower posaconazole concentrations, respectively.
Conclusions: TDM of posaconazole oral suspension formulation is recommended based on the exposure-response relationship of the present study.
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| http://dx.doi.org/10.1016/j.cca.2015.08.023 | DOI Listing |
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