Method of measuring human cyp3a inducibility

Details Method of measuring human cyp3a inducibility Method of measuring human cyp3a inducibility

C - Chemistry, Metallurgy

12

N

C12N 15/09 (2006.01) C12Q 1/02 (2006.01) C12Q 1/26 (2006.01)

Patent

CA 2482841

A method of measuring human CYP3A inducibility at the administration of a test drug characterized by comprising, to a non-human animal to which the test drug has been administered or cultured human cells having been cultured in a medium containing the test drug, transferring (A) a virus constructed by implanting a detectable reporter gene and at least 3 sites of regions capable of binding to human PXR in the non-translation region of human CYP3A gene into an adenovirus vector, and (B) a virus constructed by implanting human PXR gene into an adenovirus vector, and then measuring the expression dose of the reporter gene in the non-human animal or the cultured human cells. According to this method, the human CYP3A inducibility at the administration of a test drug to humans can be conveniently and accurately evaluated, which makes it possible to accurately evaluate the efficacy of the test drug, the expression of its side effect, the disappearance of the drug effect, etc.

L'invention concerne un procédé de mesure de l'inductibilité du CYP3A de l'homme, lors de l'administration d'un médicament d'essai un animal, ce médicament comprenant des cellules humaines cultivées dans un milieu contenant ce médicament. Ce procédé consiste à transférer (A) un virus construit en implantant un gène reporter pouvant être détecté et au moins 3 sites de zones pouvant se lier au PXR de l'homme dans la zone de non translation du gène CYP3A de l'homme dans un vecteur d'adénovirus, et (B) un virus construit en implantant un gène PXR humain dans un vecteur d'adénovirus. Ce procédé consiste ensuite à mesurer la dose d'expression du gène reporter dans l'animal ou les cellules humaines cultivées. Ce procédé permet d'évaluer avec précision l'inductibilité du CYP3A lors de l'administration d'un médicament aux hommes, ce qui permet d'évaluer avec précision l'efficacité d'un médicament, l'expression de ses effets secondaires, la disparition de l'effet du médicament, etc..

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