Method for determining therapeutic index from gene...

C - Chemistry – Metallurgy – 12 – Q

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C12Q 1/68 (2006.01) C12Q 1/02 (2006.01) C12Q 1/18 (2006.01) G01N 33/50 (2006.01)

Patent

CA 2356873

This invention provides methods for determining drug specificity, therapeutic index and effective doses for individual patients. According to the methods of the invention, graded levels of drug are applied to a biological sample or a patient. A plurality of cellular constituents are measured to determine the activity of the drug on a target pathway and at least one off-target pathway. A drug specificity is determined by comparing the target and of target activities of the drug. A therapeutic concentration (or dose) is defined as a concentration (or dose) of the drug that induces certain respone in the target pathway. A toxic concentration (or dose) is defined as a concentration (or dose) of the drug that induces certain response in the off target pathway. Therapeutic index is the ratio of the toxic concentration over therapeutic concentration. Methods are also provided to determine an effective dose of a drug for a patient by measuring the activity of the drug on the particular patient.

Cette invention se rapporte à des procédés visant à déterminer la spécificité, l'indice thérapeutique et les doses efficaces d'un médicament pour des patients différents. Conformément aux procédés de l'invention, on administre des doses graduelles de médicament à un patient ou à un échantillon biologique. On mesure une pluralité de constituants cellulaires afin d'évaluer l'activité du médicament sur une voie cible et au moins une voie hors-cible. On évalue la spécificité d'un médicament en comparant les activités cible et hors-cible dudit médicament. On définit une concentration thérapeutique (ou dose) comme étant la concentration (ou dose) qui induit une réponse donnée dans la voie hors-cible. L'indice thérapeutique est le rapport de la concentration toxique à la concentration thérapeutique. L'invention se rapporte également à des procédés visant à déterminer la dose efficace d'un médicament pour un patient et consistant à mesurer l'activité du médicament sur le patient en question.

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