The science of megestrol acetate delivery: potential to improve outcomes in cachexia
Cachexia, usually defined as the loss of >5% of an individual's baseline bodyweight over 2-6 months, occurs with a number of diseases that includes not only AIDS and advanced cancer but also chronic heart failure, rheumatoid arthritis, chronic obstructive pulmonary disease, Crohn disease, an...
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Veröffentlicht in: | BioDrugs : clinical immunotherapeutics, biopharmaceuticals, and gene therapy biopharmaceuticals, and gene therapy, 2005, Vol.19 (3), p.179-187 |
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Sprache: | eng |
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Zusammenfassung: | Cachexia, usually defined as the loss of >5% of an individual's baseline bodyweight over 2-6 months, occurs with a number of diseases that includes not only AIDS and advanced cancer but also chronic heart failure, rheumatoid arthritis, chronic obstructive pulmonary disease, Crohn disease, and renal failure. Anorexia is considered a key component of the anorexia-cachexia syndrome. Progestogens, particularly megestrol acetate, are commonly used to treat anorexia-cachexia. The mechanism of action of megestrol is believed to involve stimulation of appetite by both direct and indirect pathways and antagonism of the metabolic effects of the principal catabolic cytokines. Because the bioavailability of megestrol acetate directly affects its efficacy and safety, the formulation was refined to enhance its pharmacokinetics. Such efforts yielded megestrol acetate in a tablet form, followed by a concentrated oral suspension form, and an oral suspension form developed using nanocrystal technology. Nanocrystal technology was designed specifically to optimize drug delivery and enhance the bioavailability of drugs that have poor solubility in water. Megestrol acetate nanocrystal oral suspension is currently under review by the US FDA for the treatment of cachexia in patients with AIDS. Preclinical pharmacokinetic data suggest that the new megestrol acetate formulation has the potential to significantly shorten the time to clinical response and thus may improve outcomes in patients with anorexia-cachexia. |
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ISSN: | 1173-8804 |
DOI: | 10.2165/00063030-200519030-00004 |