29-08-2019 дата публикации
Номер: US20190264252A1
Disclosed are methods and compositions which may be used in human cytochrome P450 (CYP450) enzyme phenotyping. The methods and compositions typically utilize a mélange of substrates for different CYP450 enzymes which may be administered orally to a patient. Subsequently, the metabolites of the substrates may be detected in the patient's saliva as well as any non-metabolized substrates to calculate a metabolic ratio for any given CYP450 enzyme in order to generate a phenotypic CYP450 enzyme profile for the patient. 1. A method comprising: [{'sub': CYP1A2', 'CYP1A2', 'CYP1A2, '(i) a substrate for CYP1A2 (SUB), wherein CYP1A2 catalyzes conversion of SUBto a metabolite (MET);'}, {'sub': CYP2C19', 'CYP2C19', 'CYP2C19, '(ii) a substrate for CYP2C19 (SUB), wherein CYP2C19 catalyzes conversion of SUBto a metabolite (MET); and'}, {'sub': CYP2D6', 'CYP2D6', 'CYP2D6, '(iii) a substrate for CYP2D6 (SUB), wherein CYP2D6 catalyzes conversion of SUBto a metabolite (MET); and'}], '(a) administering to a subject in need thereof a composition comprising [{'sub': CYP1A2', 'CYP1A2, '(i) METand unconverted SUB;'}, {'sub': CYP2C19', 'CYP2C19, '(ii) METand unconverted SUB; and'}, {'sub': CYP2D6', 'CYP2D6, '(iii) METand unconverted SUB.'}], '(b) quantifying in a saliva sample from the subject2. (canceled)3. The method of claim 1 , wherein the composition is an immediate release tablet formulation of each of SUB claim 1 , SUB claim 1 , and SUBand includes a coating.47.-. (canceled)8. The method of claim 1 , wherein SUBis caffeine or theophylline.9. The method of claim 1 , wherein SUBis caffeine and METis paraxanthine.10. (canceled)11. The method of claim 1 , wherein SUBis selected from the group consisting of omeprazole claim 1 , esomeprazole claim 1 , mephenytoin claim 1 , clopidogrel claim 1 , and phenytoin.12. The method of claim 1 , wherein SUBis omeprazole and METis 50H-omeprazole claim 1 , and the composition administered in the method optionally includes a basic buffering agent.13. ...
Подробнее