Method of evaluating pharmacological effects of medicine

A method of screening pharmaceutical agents each comprising an enzyme, an enzyme inhibitor or a receptor ligand and/or prodrugs of the pharmaceutical agents, the method comprising:

• selecting a pharmaceutical agent or prodrug to be evaluated from pharmaceutical agents each comprising an enzyme, an enzyme inhibitor or a receptor ligand and/or prodrugs of the pharmaceutical agents;
• administering to a non-human subject the pharmaceutical agent or prodrug to be evaluated and a reagent comprising any one of the following substances:
• a first compound which serves as a substrate for the enzyme which is included in the pharmaceutical agent to be evaluated or for an enzyme generated from the prodrug to be evaluated, or a pharmaceutically acceptable salt thereof;
• a second compound which serves as a substrate for an enzyme which is directly inhibited by the enzyme inhibitor which is included in the pharmaceutical agent to be evaluated or by an enzyme inhibitor generated from the prodrug to be evaluated, or a pharmaceutically acceptable salt thereof;
• a third compound which serves as a substrate for an enzyme whose activity is altered by the binding between a receptor and the receptor ligand which is included in the pharmaceutical agent to be evaluated or a receptor ligand generated from the prodrug to be evaluated, or a pharmaceutically acceptable salt thereof;
• or
• a labeled form of any one of the first, second, and third compounds or salts thereof;
• collecting a biological sample from the subject at least once;
• measuring the amount of the any one of the first, second, and third compounds or salts thereof or a metabolite thereof in the biological sample;
• and
• evaluating the pharmacological effect of the pharmaceutical agent or prodrug to be evaluated based on the amount obtained in the measurement step.

A method of screening pharmaceutical agents, comprising:

• selecting a pharmaceutical agent or prodrug to be evaluated from pharmaceutical agents each comprising an enzyme, an enzyme inhibitor or a receptor ligand and/or prodrugs of the pharmaceutical agents;
• administering to a non-human subject the pharmaceutical agent or prodrug to be evaluated and a reagent comprising:
• a first compound which serves as a substrate for the enzyme which is included in the pharmaceutical agent to be evaluated or for an enzyme generated from the prodrug to be evaluated, or a pharmaceutically acceptable salt thereof;
• a second compound which serves as a substrate for a different enzyme whose activity is coupled to an activity of the enzyme which is included in the pharmaceutical agent to be evaluated oran activity of an enzyme generated from the prodrug to be evaluated, or a pharmaceutically acceptable salt thereof;
• a third compound which serves as a substrate for an enzyme which is directly inhibited by the enzyme inhibitor which is included in the pharmaceutical agent to be evaluated or by an enzyme inhibitor generated from the prodrug to be evaluated, or a pharmaceutically acceptable salt thereof;
• a fourth compound which serves as a substrate for an enzyme whose activity is coupled to an activity of an enzyme inhibitor for another enzyme, where the enzyme inhibitor is included in the pharmaceutical agent to be evaluated or coupled to an activity of an enzyme inhibitor generated from the prodrug to be evaluated, or a pharmaceutically acceptable salt thereof;
• a fifth compound which serves as a substrate for an enzyme whose activity is altered by the binding between a receptor and the receptor ligand which is included in the pharmaceutical agent to be evaluated or a receptor ligand generated from the prodrug to be evaluated, or a pharmaceutically acceptable salt thereof;
• or
• a labeled form of any one of the first to fifth compounds,
• wherein the enzyme for which the first compound is a substrate comprises amylase, the enzyme for which the third compound is a substrate comprises dihydroxyphenvialanine (DOPA) decarboxylase, α-glucosidase, or pancreatic protease, or the enzyme for which the fifth compound is a substrate comprises an ornithine metabolic enzyme;
• collecting a biological sample from the subject at least once;
• measuring the amount of the any one of the first to fifth compounds, a pharmaceutically acceptable salt thereof, or a metabolite thereof in the biological sample;
• and
• evaluating the pharmacological effect of the pharmaceutical agent or prodrug to be evaluated based on the amount obtained in the measurement step.