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Systemic Fungal Infections (systemic + fungal_infections)
Selected AbstractsInvestigating Carboxylic Acid Analogues of Ambruticin through Semi-SynthesisCHEMMEDCHEM, Issue 10 2006Yuan Xu Systemic fungal infections have increased significantly in recent years and this is important particularly for immunocompromised patients. A series of ambruticin carboxylic acid analogues have been synthesised through semi-synthesis and tested for their antifungal activity. The results suggest that the carboxylic acid is not crucial for potency, with the tetrazole 16 analogue showing similar antifungal activity to ambruticin VS-3 4. [source] Itraconazole oral solution and intravenous formulations: a review of pharmacokinetics and pharmacodynamicsJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 3 2001L. Willems Itraconazole is a triazole antifungal agent with a broad spectrum of activity. It is well tolerated and highly efficacious, particularly because its main metabolite, hydroxy-itraconazole, also has considerable antifungal activity. Two new formulations of itraconazole, an oral solution and an intravenous formulation, have recently been developed, which combine lipophilic itraconazole with cyclodextrin. These formulations have improved the solubility of itraconazole, leading to enhanced absorption and bioavailability compared with the original capsule formulation, without having an impact on the tolerability profile of itraconazole. The oral solution and intravenous formulations of itraconazole produce consistent plasma concentrations and are ideal for the treatment of systemic fungal infections in a wide range of patient populations. The additional flexibility offered by the different routes of administration means that itraconazole treatment can be specifically tailored for use in all patients, including children and those requiring intensive care. [source] Amphotericin B formulations and drug targetingJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2008J.J. Torrado Abstract Amphotericin B is a low-soluble polyene antibiotic which is able to self-aggregate. The aggregation state can modify its activity and pharmacokinetical characteristics. In spite of its high toxicity it is still widely employed for the treatment of systemic fungal infections and parasitic disease and different formulations are marketed. Some of these formulations, such as liposomal formulations, can be considered as classical examples of drug targeting. The pharmacokinetics, toxicity and activity are clearly dependent on the type of amphotericin B formulation. New drug delivery systems such as liposomes, nanospheres and microspheres can result in higher concentrations of AMB in the liver and spleen, but lower concentrations in kidney and lungs, so decreasing its toxicity. Moreover, the administration of these drug delivery systems can enhance the drug accessibility to organs and tissues (e.g., bone marrow) otherwise inaccessible to the free drug. During the last few years, new AMB formulations (AmBisome®, Abelcet®, and Amphotec®) with an improved efficacy/toxicity ratio have been marketed. This review compares the different formulations of amphotericin B in terms of pharmacokinetics, toxicity and activity and discusses the possible drug targeting effect of some of these new formulations. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:2405,2425, 2008 [source] Frequency of potential azole drug,drug interactions and consequences of potential fluconazole drug interactions,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 11 2005D. Tony Yu MD Abstract Purpose To assess the frequency of potential azole,drug interactions and consequences of interactions between fluconazole and other drugs in routine inpatient care. Methods We performed a retrospective cohort study of hospitalized patients treated for systemic fungal infections with an oral or intravenous azole medication between July 1997 and June 2001 in a tertiary care hospital. We recorded the concomitant use of medications known to interact with azole antifungals and measured the frequency of potential azole drug interactions, which we considered to be present when both drugs were given together. We then performed a chart review on a random sample of admissions in which patients were exposed to a potential moderate or major drug interaction with fluconazole. The list of azole-interacting medications and the severity of interaction were derived from the DRUGDEX® System and Drug Interaction Facts. Results Among the 4185 admissions in which azole agents (fluconazole, itraconazole or ketoconazole) were given, 2941 (70.3%) admissions experienced potential azole,drug interactions, which included 2716 (92.3%) admissions experiencing potential fluconazole interactions. The most frequent interactions with potential moderate to major severity were co-administration of fluconazole with prednisone (25.3%), midazolam (17.5%), warfarin (14.7%), methylprednisolone (14.1%), cyclosporine (10.7%) and nifedipine (10.1%). Charts were reviewed for 199 admissions in which patients were exposed to potential fluconazole drug interactions. While four adverse drug events (ADEs) caused by fluconazole were found, none was felt to be caused by a drug,drug interaction (DDI), although in one instance fluconazole may have contributed. Conclusions Potential fluconazole drug interactions were very frequent among hospitalized patients on systemic azole antifungal therapy, but they had few apparent clinical consequences. Copyright © 2005 John Wiley & Sons, Ltd. [source] Microbial natural products as a source of antifungalsCLINICAL MICROBIOLOGY AND INFECTION, Issue 1 2003M. F. Vicente The vast number and variety of chemotherapeutic agents isolated from microbial natural products and used to treat bacterial infections have greatly contributed to the improvement of human health during the past century. However, only a limited number of antifungal agents (polyenes and azoles, plus the recently introduced caspofungin acetate) are currently available for the treatment of life-threatening fungal infections. Furthermore, the prevalence of systemic fungal infections has increased significantly during the past decade. For this reason, the development of new antifungal agents, preferably with novel mechanisms of action, is an urgent medical need. A selection of antifungal agents in early stages of development, produced by micro-organisms, is summarized in this review. The compounds are classified according to their mechanisms of action, covering inhibitors of the synthesis of cell wall components (glucan, chitin and mannoproteins), of sphingolipid synthesis (serine palmitoyltransferase, ceramide synthase, inositol phosphoceramide synthase and fatty acid elongation) and of protein synthesis (sordarins). In addition, some considerations related to the chemotaxonomy of the producing organisms and some issues relevant to antifungal drug discovery are also discussed. [source] | |||||||||||||