Methods to evaluate cytochrome p450 2c19 isoenzyme activity using a breath test

Abstract

The present invention relates, generally to a method of determining and assessing cytochrome P450 2C19-related (CYP2C19) metabolic capacity in an individual mammalian subject via a breath assay, by determining the relative amount of 13 CO 2 exhaled by the subject upon intravenous or oral administration of a 13 C-labeled CYP2C19 substrate compound. The present invention is useful as anon-invasive, in vivo assay for evaluating CYP2C19 enzyme activity in a subject using the metabolite 13 CO 2 in expired breath, to phenotype individual subjects and to determine the selection, optimal dosage and timing of drug administration.

1 - 29 . (canceled) 
     
     
         30 . A method of selecting a mammalian subject for inclusion in a clinical trial for determining the efficacy of a compound to prevent or treat a medical condition, comprising the steps of:
 (a) administering a  13 C-labeled cytochrome P450 2C19 isoenzyme substrate compound to the subject;   (b) measuring a metabolite excretion pattern of an isotope-labeled metabolite excreted from the body of the subject;   (c) comparing the obtained metabolite excretion pattern in the subject to a reference standard excretion pattern;   (d) classifying the subject according to a metabolic phenotype selected from the group consisting of: poor metabolizer, intermediate metabolizer, extensive metabolizer, and ultrarapid metabolizer, based on the obtained metabolite excretion pattern; and   (e) selecting the subject classified as extensive metabolizer in step (d) for inclusion in the clinical trial.   
     
     
         31 . The method according to  claim 30 , wherein the isotope-labeled metabolite excreted from the body of the subject is isotope-labeled CO 2  in the expired air. 
     
     
         32 . A kit comprising a  13 C-labeled cytochrome P450 2C19 isoenzyme substrate compound and instructions provided with the substrate that describe how to determine  13 C-labeled cytochrome P450 2C19 isoenzyme substrate compound metabolism in a subject. 
     
     
         33 . The kit according to  claim 32 , further comprising at least three breath collection bags. 
     
     
         34 . The kit of according to  claim 32 , further comprising a cytochrome P450 2C19 modulating agent.