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Phenotyping Cytochrome P450 1A2 in Humans: Concepts in Drug Metabolism, Individualized Medicine, and Bioethics
Author(s) -
Fletke Kyle Jordan,
Furge Laura Lowe
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a216-b
Subject(s) - paraxanthine , cyp1a2 , cytochrome p450 , urine , caffeine , chemistry , drug metabolism , metabolism , pharmacology , high performance liquid chromatography , biochemistry , chromatography , medicine
Cytochrome P450 enzymes are a family of heme‐containing proteins located throughout the body with roles in metabolism of endogenous and exogenous compounds including nearly all pharmaceutical agents. The activity of the different cytochrome P450 enzymes varies among individuals and thus affects metabolism of foreign compounds. The goal of this study was to assess P450 1A2 metabolic activity by measuring caffeine and paraxanthine present in human urine following consumption of caffeine using isocratic reverse‐phase HPLC. Paraxanthine detected in all collected urine samples ranged in concentration from 1.93 μg/mL to 51.98 μg/mL. Caffeine was detected in most urine samples and ranged in concentration from 0.70 μg/mL to 77.17 μg/mL. The metabolic ratio of each urine sample at each time point was determined using the relationship MR = [paraxanthine]/[caffeine]. The range for MR values found was 0.34 and 26.34 and these values are within the ranges described in the literature by many groups and with much larger sample size. This laboratory exercise provides a means for simple assessment of P450 1A2 metabolic activity using a direct HPLC method and introduces students to the complexities of individualized medicine as well as the basic biochemical techniques of sample preparation and quantitative HPLC. (Supported in part by: Dreyfus Foundation, Kalamazoo College Kaufmann Fund, Michigan Economic Development Corporation).