US 5,478,723 AGranted

Method and apparatus for determining the role of cytochrome P450 and related enzymes in the metabolism of drugs and other chemicals

OwnerAndrew Parkinson, Dorn C. Cookinventors

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Abstract

A method and apparatus for determining the enzyme or enzymes in the human body which metabolize a particular drug. Microsomes are obtained from each of several donors. The microsome for one donor is reacted with a test drug and the quantity of metabolites produced is determined. The microsomes are similarly each reacted with the test drug and the quantity of metabolites produced for each microsome is determined to generate drug metabolism data. The drug metabolism data obtained is compared to reference data which indicates the activity of a select number of major enzymes in each of the donors. The reference data for each enzyme is separately tabulated. The enzyme responsible for the metabolism of the test drug is identified when the metabolism data correlates with the tabulated reference data for that enzyme.

Claims2

Dependent claims

A method for determining whether an enzyme in the human body metabolizes a drug, comprising the steps of

(a) providing for the enzyme a reference data tabulation quantifying the activity of the enzyme in the body of each of a plurality of donors, the activity of the enzyme in one of said donors being different from the activity of the enzyme in each of the other of said donors, the activity of the enzyme in said one of said donors with respect to the activity of the enzyme in each of the other of said donors defining a first proportional relationship;
(b) providing from the body of each of said plurality of donors a donor sample of enzymes, each of said donor samples
(i) being generated from the same type of body tissue, and
(ii) having a known weight of the enzyme;
(c) generating drug metabolism data representing the rate of metabolism of the drug by one of said donor samples, said drug metabolism data being generated by
(i) contacting a fixed quantity of said drug with said one of said donor samples for a selected period of time to produce a reaction mixture;
(ii) analyzing said reaction mixture to determine the quantity of metabolites present per unit weight of the enzyme in said one of said donor samples;
(d) repeating step (c) for each of the remaining ones of said donor samples, said quantity of metabolites present in said reaction mixture for said one of said donor samples with respect to the quantity of metabolites present in said reaction mixture for each of the other of said donor samples defining a second proportional relationship;
(e) comparing said second proportional relationship to said first proportional relationship to determine if said second proportional relationship corresponds within designated limits to said first proportional relationship.

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Dependencies are inferred from the claim text.