Saptaparna Pal, Amity University Kolkata
Posaconazole is the latest antifungal agent to be approved for use in Canada against severe fungal infections. With excellent and intensive activity against a large spectrum of fungi as well as yeasts, as well as having a well-formulated oral formulation, posaconazole provides many possible advantages.
Amphotericin B, whether in lipid-based or deoxycholate formulation, is an endovenous medication with the most versatile spectrum of activity of any antifungal agent. Although, its use is accelerated with a high rate of infusion reactions and nephrotoxicity; the intensifying fungal disease has occurred in patients who were not able to complete treatment. Similar to all triazoles, posaconazole restricts the fungal lanosterol 14 alpha- demethylase enzyme(CYP51), a new member of the cytochrome P450 family. As a result, posaconazole blocks the synthesis of ergosterol, the basic sterol in the fungal cell membrane integrity, and a crucial determinant of cell membrane integrity membrane-associated protein function and progression through the cell cycle.
Posaconazole is administered as an oral suspension at a dose of about 800mg per day; no parenteral formulation is recently available. As, high-fat meals, nutritional supplements and frequent administration all three supports the absorption of posaconazole, the 800mg dose is divided twice daily if the patient is intaking enteral nutrition, and four times daily if not. In the case of fasting individually, the most common steady-state plasma cone is 0.5mg/L based on four times daily dosing, it is a bit higher at 0.72mg/L when taken twice daily with a high-fat meal or nutritional supplement. Posaconazole has also shown to be at least as effective as Amphotericin B in the case of human blood trials for IFS and murine. Posaconazole is one of the recent remedies against mucormycosis and zygomycosis. Posaconazole is also more active in vitro against a wide range of filamentous fungi than in voriconazole. Posaconazole has a half-life of 35 h and is removed unchanged through the gastrointestinal tract. Because the kidneys play a short role in the excretion of posaconazole, no dose adjustment is necessary, even in cases of severe renal impairment. Posaconazole restricts the hepatic CYP3A4 enzyme, a member of the cytochrome P450 enzyme system; therefore, it may increase the serum concentrations of drugs with which it is coadministered, including tacrolimus and cyclosporine.
Despite the diverse spectrum of activity indicated by in vitro and in vivo experimental data, posaconazole has got Canadian approval only for the treatment of OPC and refractory invasive aspergillus, as well as for the prophylaxis of invasive aspergillus and also candidiasis in high-risk patients. Posaconazole is now the recommended and accepted prophylactic regimen for use in high-risk patients, but its cost may restrict its use. In terms of other IFIs, along with its tolerated oral formulation and few drug interactions, posaconazole may become the agent of choice for long-term aid of the opportunistic mycoses against which voriconazole has restricted activity, including mucormycosis. However, the high barrier to the resistance created by posaconazole’s unique structure may confirm its niche in treating polyene, -echinocandin, and even triazole resistance IFIs.
Also read: LOXHD1: A gene crucial for understanding hereditary deafness
References: Page, Andrea V, and W Conrad Liles. “Posaconazole: A new agent for the prevention and management of severe, refractory or invasive fungal infections.” The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale vol. 19, 4 (2008): 297-305. doi:http://10.1155/2008/825901
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