Pharmacokinetic regulation of caffeine consumption linked to genetic polymorphism

More details can be found in the text.

EnzymeBiologic RoleClinical RelevanceReplicationLocation in Text
CYP1A1CYP1A1 metabolizesAssociation with habitual caffeine consumptionYesIV.A.4
– caffeine to paraxanthine, theobromine and 1,3,7-TMU
– polycyclic aromatic hydrocarbons, which are important constituents of coffee
CYP1A2Major enzyme involved in liver caffeine metabolismAssociation with habitual caffeine consumptionYesIV.A.1
CYP2A6Metabolism of paraxanthine to 1,7-DMUNo clear link with consumption shown yetYesIV.A.1
NAT2Metabolism of paraxanthine to AFMUNo clear link with consumption shown yetYesIV.A.2
XOMetabolism of 1-MX to 1-MU1MU:1MX ratio used following caffeine administration as a pharmacodynamic measure of drug effect on XO activityYesIV.A.3
  • AFMU, 5-acetylamino-6-formylamino-3-methyluracil; CYP, cytochrome P450 followed by the number corresponding to each specific isoform; NAT2, N-acetyltransferase-2; XO, xanthine oxidase; 1,3,7-TMU, 1,3,7-trimethyluric acid; 1,7-DMU, 1,7-dimethyluric acid; 1-MX, 1-methylxanthine; 1-MU, 1-methyluric acid.