Method and compositions for administering taxanes orally to...

A - Human Necessities – 61 – P

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A61P 35/00 (2006.01) A61K 31/335 (2006.01) A61K 31/337 (2006.01) A61K 47/42 (2006.01) A61K 47/44 (2006.01)

Patent

CA 2389583

Taxane antineoplastic agents which have heretofore exhibited poor or non- existent oral bioavailability are administered orally to human patients suffering from taxane-responsive disease conditions and made sufficiently bioavailable to achieve therapeutic blood levels. In a preferred embodiment, the taxane, preferably paclitaxel, is co-administered to the patient with an oral cyclosporin enhancing agent, preferably cyclosporin A. By one preferred method, a dose of oral enhancer is administered about 0.5-72 hours before the taxane and a second dose of the enhancer and administered immediately before, together with or immediately after the taxane. A method of treating human patients suffering from taxane-responsive disease conditions is also provided, as well as a method for providing such treatment while preventing or reducing hypersensitivity and allergic reactions without the need for pre-medication.

L'invention concerne des agents antinéoplasiques à base de taxane qui jusqu'alors présentaient une biodisponibilité faible ou inexistante, administrés par voie orale à des patients humains souffrant d'états pathologiques répondant à la taxane, rendus suffisamment biodisponibles pour atteindre des concentrations sanguines à effet thérapeutiques. Dans un mode de réalisation recommandé, la taxane, de préférence du paclitaxel, est co-administrée au patient avec un agent facilitant de cyclosporine, de préférence de cyclosporine A. Un mode de réalisation recommandé consiste à administrer une dose d'agent facilitant oral entre 0,5 et 72 heures environ avant la taxane, et une seconde dose, immédiatement avant, en même temps ou immédiatement après la taxane. L'invention concerne également une méthode de traitement de patients souffrant d'états pathologiques répondant à la taxane, ainsi qu'une méthode d'administration du traitement tout en empêchant ou en réduisant les réactions d'hypersensibilité ou d'allergie sans l'aide de prémédication

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