Details of the Drug Metabolized by Drug-Metabolizing Enzyme (DME)

General Information of Drug (ID: DR0257)
Drug Name
Caffeine
Synonyms
Cafeina; Caffedrine; Caffein; Caffeine, synthetic; Caffine; Cafipel; Coffein; Coffeine; Coffeinum; Caffeine citrate; DHCplus; Dexitac; Durvitan; Eldiatric C; Guaranine; Hycomine; Koffein; Mateina; Methyltheobromide; Methyltheobromine; Nix Nap; No-Doz; Nodaca; Organex; Phensal; Quick-Pep; Refresh'n; Stim; Thein; Theine; Theophylline, 7-methyl; Tirend; Vivarin; Wigraine; caffeine; Caffeina citrate; Caffeine citrate (1:1); Caffeine citrated; Caffeine, Citrated; Citrated caffein; Citric acid, compd. with caffeine (1:1); DSSTox_CID_26938; DSSTox_GSID_46938; DSSTox_RID_82023; NCGC00015208-09; U26EO4675Q; UNII-U26EO4675Q; 1,2,3-Propanetricarboxylic acid, 2-hydroxy-, mixt. with 3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione; 1,2,3-Propanetricarboxylic acid,2-hydroxy-,compounds,mixt. with 3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6- dione; 69-22-7; C8H10N4O2.C6H8O7; CAS-69-22-7; 1,3,7-Trimethyl-2,6-dioxopurine; 1,3,7-Trimethylxanthine; 1958/8/2; 3,7-Dihydro-1,3,7-trimethyl-1H-purine-2,6-dione; 7-Methyltheophylline; Alert-pep; Anhydrous caffeine; Cafamil; Cafecon
Indication Orthostatic hypotension [ICD11: BA21] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 194.19 Topological Polar Surface Area 58.4
Heavy Atom Count 14 Rotatable Bond Count 0
Hydrogen Bond Donor Count 0 Hydrogen Bond Acceptor Count 3
Cross-matching ID
PubChem CID
2519
PubChem SID
9684 ; 71207 ; 589166 ; 597401 ; 820671 ; 830649 ; 842006 ; 866261 ; 3132319 ; 5635243 ; 7847594 ; 7886558 ; 7978841 ; 8026209 ; 8139831 ; 8144467 ; 8149227 ; 8151672 ; 10528151 ; 10560612 ; 11110907 ; 11110908 ; 11120353 ; 11120841 ; 11121329 ; 11335905 ; 11361144 ; 11364195 ; 11366757 ; 11369319 ; 11371241 ; 11375461 ; 11377481 ; 11455699 ; 11462116 ; 11484958 ; 11489077 ; 11490137 ; 11493596 ; 11495115 ; 11528255 ; 11535451 ; 11537628 ; 14772978 ; 17389997 ; 17404791 ; 21317890 ; 24277682 ; 24856687 ; 24886771
ChEBI ID
ChEBI:27732
CAS Number
58-08-2
TTD Drug ID
D0B3HD
Formula
C8H10N4O2
Canonical SMILES
CN1C=NC2=C1C(=O)N(C(=O)N2C)C
InChI
1S/C8H10N4O2/c1-10-4-9-6-5(10)7(13)12(3)8(14)11(6)2/h4H,1-3H3
InChIKey
RYYVLZVUVIJVGH-UHFFFAOYSA-N
The Metabolic Roadmap of This Drug
The Full List of Drug Metabolites (DM) of This Drug
DM Name DM ID PubChem ID Reaction DM Level REF
1,3,7-Trimethyluric acid DM000526
79437
Oxidation - 8-Hydroxylation 1 [4] , [11]
Paraxanthine DM000523
4687
Oxidation - Demethylation 1 [12] , [11]
Theobromine DM000527
5429
Oxidation - 1-N-Demethylation 1 [4] , [11]
Theophylline DM003086
2153
Oxidation - 7-N-Demethylation 1 [4] , [11]
1,7-Dimethyluric acid DM000524
91611
Oxidation - 3-N-Demethylation 2 [4] , [11]
1-Methylxanthine DM000521
80220
Oxidation - 7-N-Demethylation 2 [9] , [11]
1-Methylxanthine DM000521
80220
Oxidation - 3-N-Demethylation 2 [9] , [11]
5-Acetylamino-6-formylamino-3-methyluracil DM000525
108214
Unclear 2 [9] , [11]
1-Methyluric acid DM000522
69726
Oxidation - Oxidation 3 [9] , [11]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR000543 Caffeine Paraxanthine Oxidation - Demethylation CYP1A2 [12], [11]
MR000544 Caffeine 1,3,7-Trimethyluric acid Oxidation - 8-Hydroxylation CYP1A2 ... [4], [11]
MR000545 Caffeine Theobromine Oxidation - 1-N-Demethylation CYP1A2 ... [4], [11]
MR000546 Caffeine Theophylline Oxidation - 7-N-Demethylation CYP1A2 ... [4], [11]
MR000540 Paraxanthine 1-Methylxanthine Oxidation - 7-N-Demethylation XDH [9], [11]
MR000541 Paraxanthine 1,7-Dimethyluric acid Oxidation - 3-N-Demethylation CYP1A2 [4], [11]
MR000542 Paraxanthine 5-Acetylamino-6-formylamino-3-methyluracil Unclear NAT2 [9], [11]
MR000547 Theophylline 1-Methylxanthine Oxidation - 3-N-Demethylation CYP1A2 [9], [11]
MR000539 1-Methylxanthine 1-Methyluric acid Oxidation - Oxidation XDH [9], [11]
⏷ Show the Full List of 9 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cytochrome P450 1A2 (CYP1A2) DME0003 Homo sapiens
CP1A2_HUMAN
1.14.14.1
[2]
Cytochrome P450 1B1 (CYP1B1) DME0023 Homo sapiens
CP1B1_HUMAN
1.14.14.1
[3]
Cytochrome P450 2C8 (CYP2C8) DME0018 Homo sapiens
CP2C8_HUMAN
1.14.14.1
[4]
Cytochrome P450 2C9 (CYP2C9) DME0019 Homo sapiens
CP2C9_HUMAN
1.14.14.1
[5]
Cytochrome P450 2D6 (CYP2D6) DME0009 Homo sapiens
CP2D6_HUMAN
1.14.14.1
[6]
Cytochrome P450 2E1 (CYP2E1) DME0013 Homo sapiens
CP2E1_HUMAN
1.14.14.1
[7]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[8]
N-acetyltransferase 2 (NAT2) DME0051 Homo sapiens
ARY2_HUMAN
2.3.1.5
[9]
RNA cytidine acetyltransferase (hALP) DME0007 Homo sapiens
NAT10_HUMAN
2.3.1.5
[10]
Xanthine dehydrogenase/oxidase (XDH) DME0070 Homo sapiens
XDH_HUMAN
1.17.1.4
[9]
⏷ Show the Full List of 10  DME(s)
References
1 Obeticholic Acid was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
3 Oxidation of xenobiotics by recombinant human cytochrome P450 1B1. Drug Metab Dispos. 1997 May;25(5):617-22.
4 PharmGKB summary: caffeine pathway. Pharmacogenet Genomics. 2012 May;22(5):389-95.
5 Monkey liver cytochrome P450 2C9 is involved in caffeine 7-N-demethylation to form theophylline. Xenobiotica. 2013 Dec;43(12):1037-42.
6 Determinants of interindividual variability and extent of CYP2D6 and CYP1A2 inhibition by paroxetine and fluvoxamine in vivo. J Clin Psychopharmacol. 1998 Jun;18(3):198-207.
7 CYP2E1 active site residues in substrate recognition sequence 5 identified by photoaffinity labeling and homology modeling. Arch Biochem Biophys. 2007 Mar 1;459(1):59-69.
8 Effect of cytochrome P450 (CYP) inducers on caffeine metabolism in the rat. Pharmacol Rep. 2007 May-Jun;59(3):296-305.
9 In vivo evaluation of CYP1A2, CYP2A6, NAT-2 and xanthine oxidase activities in a Greek population sample by the RP-HPLC monitoring of caffeine metabolic ratios Biomed Chromatogr. 2007 Feb;21(2):190-200. doi: 10.1002/bmc.736.
10 A population and family study of N-acetyltransferase using caffeine urinary metabolites. Clin Pharmacol Ther. 1993 Aug;54(2):134-41.
11 Urine caffeine metabolites are positively associated with cognitive performance in older adults: An analysis of US National Health and Nutrition Examination Survey (NHANES) 2011 to 2014. Nutr Res. 2023 Jan;109:12-25. doi: 10.1016/j.nutres.2022.11.002.
12 Pharmacokinetic analysis and comparison of caffeine administered rapidly or slowly in coffee chilled or hot versus chilled energy drink in healthy young adults Clin Toxicol (Phila). 2016;54(4):308-12. doi: 10.3109/15563650.2016.1146740.

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