POSACONAZOLE: Pharmacology and drug interactions
Author:
Dr Helen Sambatakou
Date: 25 September 2002
Abstract:
Systemic fungal infections have been recognised as a major cause of morbidity and mortality during the last two decades. Moreover, the treatment of serious fungal infections, especially aspergillosis, is still far from satisfactory and although improving, remains poor. Established azole antifungals have several limitations in terms of potency, spectrum, inherent or acquired resistance, pharmacokinetic profile and drug-drug interactions. The diversity of underlying immunocompromised factors of people affected with fungal infections (premature birth, congenital immune deficiencies, such as chronic granulomatous disease, surgery, diabetes, HIV infection, transplantation), as well as the complexity of various treatment regimens these populations receive (chemotherapy, anti-rejection drugs, antiretrovirals etc) make the use of antifungals in these medically complex patients challenging. Several new antifungals, including novel compounds of familiar classes, as well as new classes with new targets of mechanisms are in various stages of development. Posaconazole [ SCH 56592, Schering-Plough Research Institute (SPRI), Kenilworth, New Jersey, USA] is a broad spectrum third generation triazole with some structural similarities to ITZ (fig 1). It is in the late stages of clinical development (in phase III clinical studies). It has extremely promising potency for many fungi including Aspergillus spp. and a broad spectrum of activity based on accumulated in vitro and murine model data. Posaconazole (POZ) is under investigation for oral administration, and close analogues may allow IV administration in the future.
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