Abstract
BIOANALYTICAL METHOD VALIDATION AND EFFECT OF GRADED DOSES OF PIPERINE ON PHARMACOKINETIC PARAMETERS OF POSACONAZOLE USING LCMS-MS METHOD

Satish Gabhe*, Susmita Bhandugare and Ashwini Pharne

ABSTRACT

In recent years, the antifungal triazole, posaconazole has become increasingly important as a prophylatic and for treatment of systemic mycoses. Whether therapeutic drug monitoring can reduce the risk of treatment failures by avoiding sub-therapeutic plasma concentrations needs further examination. Based on the ability of posaconazole to inhibit cytochrome P450 3A4, several drug interactions can be expected, especially with agents that undergo extensive first-pass effect through the gut and the liver. However, more information is needed regarding dose modifications during concomitant administration of posaconazole with drugs in certain categories, such as vinca alkaloids and retinoids. In Europe, the drug has been approved for the treatment of invasive fungal infection (IFI), including second-line treatment of aspergillosis, fusariosis, chromoblastomycosis, mycetoma and coccidioidomycosis. Posaconazole is also approved for antifungal prophylaxis in neutropenic high-risk patients with acute myelogenous leukaemia (AML) or myelodysplastic syndrome (MDS) who are receiving cytotoxic chemotherapy and in immunosuppressed patients with graft-versus-host disease (GVHD) after peripheral blood stem cell transplant (PBSCT).[1] Posaconazole has enhanced activity against many old, new, and emerging fungal pathogens compared with the activities of other azoles and caspofungin (an echinocandin). Numerous in-vitro studies demonstrate that posaconazole has a broad spectrum of activity against majority of yeasts, filamentous fungi, and azole-resistant Candida species.[2,3] During the second wave of COVID-19, posaconazole was used to treat COVID-19 associated mucormycosis.[4]

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