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

General Information of Drug (ID: DR0282)
Drug Name
Carvedilol
Synonyms
Carvedilolum; Carvedilolum [Latin]; Coreg CR; DQ 2466; Dilatrend; Eucardic; SKF 105517; carvedilol; (+-)-1-(Carbazol-4-yloxy)-3-((2-(o-methoxyphenoxy)ethyl)amino)-2-propanol; 1-((9H-Carbazol-4-yl)oxy)-3-((2-(2-methoxyphenoxy)ethyl)amino)propan-2-ol; 1-(9H-Carbazol-4-yloxy)-3-[[2-(2-methoxyphenoxy)ethyl]amino]-2-propanol; 1-(9H-carbazol-4-yloxy)-3-[2-(2-methoxyphenoxy)ethylamino]propan-2-ol; 72956-09-3; BM 14190; BM-14190; C24H26N2O4; CHEBI:3441; CHEMBL723; Coreg; HSDB 7044
Indication Congestive heart failure [ICD11: BD10] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 406.5 Topological Polar Surface Area 75.7
Heavy Atom Count 30 Rotatable Bond Count 10
Hydrogen Bond Donor Count 3 Hydrogen Bond Acceptor Count 5
Cross-matching ID
PubChem CID
2585
PubChem SID
9092 ; 7387304 ; 7847321 ; 7978866 ; 8151709 ; 11364559 ; 11367121 ; 11369683 ; 11372422 ; 11374391 ; 11377845 ; 11485621 ; 11489489 ; 11490997 ; 11492451 ; 11495479 ; 11528712 ; 12013067 ; 14855122 ; 26719722 ; 26719723 ; 29221745 ; 46386749 ; 46386871 ; 46505146 ; 47805057 ; 48415707 ; 49681735 ; 49834917 ; 50112972 ; 50112973 ; 53789407 ; 56313592 ; 56413047 ; 56464135 ; 57321386 ; 76450239 ; 81040900 ; 81092790 ; 85209910 ; 85789499 ; 85789708 ; 87560280 ; 90341342 ; 92251378 ; 92307922 ; 92308493 ; 92308705 ; 92711411 ; 103197484
ChEBI ID
ChEBI:3441
CAS Number
72956-09-3
TTD Drug ID
D0W9LX
Formula
C24H26N2O4
Canonical SMILES
COC1=CC=CC=C1OCCNCC(COC2=CC=CC3=C2C4=CC=CC=C4N3)O
InChI
1S/C24H26N2O4/c1-28-21-10-4-5-11-22(21)29-14-13-25-15-17(27)16-30-23-12-6-9-20-24(23)18-7-2-3-8-19(18)26-20/h2-12,17,25-27H,13-16H2,1H3
InChIKey
OGHNVEJMJSYVRP-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-hydroxyphenylcarvedilol DM000745
182523
Oxidation - 1-Hydroxylation 1 [2]
4'-hydroxyphenylcarvedilol DM000739
4572774
Oxidation - 4'-Hydroxylation 1 [2]
5'-hydroxyphenylcarvedilol DM000741
4181439
Oxidation - 5'-Hydroxylation 1 [2]
8-hydroxycarbazolylcarvedilol DM000737
9979639
Oxidation - 8-Hydroxylation 1 [2]
Carvedilol glucuronide DM000747
129627137
Conjugation - O-Glucuronidation 1 [2]
O-Desmethylcarvedilol DM000743
155763
Oxidation - O-Demethylation 1 [2]
Carvedilol metabolite M15 DM000746 N. A. Conjugation - Glucuronidation 2 [2]
Carvedilol metabolite M17 DM000738 N. A. Conjugation - Glucuronidation 2 [2]
Carvedilol metabolite M29 DM000740 N. A. Conjugation - Glucuronidation 2 [2]
Carvedilol metabolite M30 DM000742 N. A. Conjugation - Glucuronidation 2 [2]
Carvedilol metabolite M3a/b DM000744 N. A. Conjugation - Glucuronidation 2 [2]
⏷ Show the Full List of 11  DM(s)
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR000569 Carvedilol 8-hydroxycarbazolylcarvedilol Oxidation - 8-Hydroxylation CYP1A1 ... [2]
MR000570 Carvedilol 4'-hydroxyphenylcarvedilol Oxidation - 4'-Hydroxylation CYP2D6 ... [2]
MR000571 Carvedilol 5'-hydroxyphenylcarvedilol Oxidation - 5'-Hydroxylation CYP2D6 ... [2]
MR000572 Carvedilol O-Desmethylcarvedilol Oxidation - O-Demethylation CYP2C9 ... [2]
MR000573 Carvedilol 1-hydroxyphenylcarvedilol Oxidation - 1-Hydroxylation PTGS1 ... [2]
MR000574 Carvedilol Carvedilol glucuronide Conjugation - O-Glucuronidation UGT1A1 ... [2]
MR000568 1-hydroxyphenylcarvedilol Carvedilol metabolite M15 Conjugation - Glucuronidation Unclear [2]
MR000565 4'-hydroxyphenylcarvedilol Carvedilol metabolite M29 Conjugation - Glucuronidation Unclear [2]
MR000566 5'-hydroxyphenylcarvedilol Carvedilol metabolite M30 Conjugation - Glucuronidation Unclear [2]
MR000564 8-hydroxycarbazolylcarvedilol Carvedilol metabolite M17 Conjugation - Glucuronidation Unclear [2]
MR000567 O-Desmethylcarvedilol Carvedilol metabolite M3a/b Conjugation - Glucuronidation Unclear [2]
⏷ Show the Full List of 11 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cytochrome P450 1A1 (CYP1A1) DME0006 Homo sapiens
CP1A1_HUMAN
1.14.14.1
[2]
Cytochrome P450 1A2 (CYP1A2) DME0003 Homo sapiens
CP1A2_HUMAN
1.14.14.1
[3]
Cytochrome P450 2C9 (CYP2C9) DME0019 Homo sapiens
CP2C9_HUMAN
1.14.14.1
[4]
Cytochrome P450 2D6 (CYP2D6) DME0009 Homo sapiens
CP2D6_HUMAN
1.14.14.1
[5]
Cytochrome P450 2E1 (CYP2E1) DME0013 Homo sapiens
CP2E1_HUMAN
1.14.14.1
[6]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[7]
Prostaglandin G/H synthase 1 (COX-1) DME0091 Homo sapiens
PGH1_HUMAN
1.14.99.1
[2]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DME0004 Homo sapiens
UD11_HUMAN
2.4.1.17
[8]
UDP-glucuronosyltransferase 2B4 (UGT2B4) DME0047 Homo sapiens
UD2B4_HUMAN
2.4.1.17
[2]
UDP-glucuronosyltransferase 2B7 (UGT2B7) DME0040 Homo sapiens
UD2B7_HUMAN
2.4.1.17
[8]
Unclear metabolic mechanism (DME-unclear) DME1251 Bacteroides fragilis Not Available Not Available [9]
Unclear metabolic mechanism (DME-unclear) DME1254 Bacteroides thetaiotaomicron Not Available Not Available [9]
Unclear metabolic mechanism (DME-unclear) DME1256 Bacteroides sartorii Not Available Not Available [9]
Unclear metabolic mechanism (DME-unclear) DME1364 Bacteroides coprophilus Not Available Not Available [9]
Unclear metabolic mechanism (DME-unclear) DME1365 Bacteroides dorei Not Available Not Available [9]
Unclear metabolic mechanism (DME-unclear) DME1376 Bacteroides ovatus Not Available Not Available [9]
Unclear metabolic mechanism (DME-unclear) DME1385 Bacteroides xylanisolvens Not Available Not Available [9]
Unclear metabolic mechanism (DME-unclear) DME1393 Blautia hansenii Not Available Not Available [9]
Unclear metabolic mechanism (DME-unclear) DME1404 Clostridium sporogenes Not Available Not Available [9]
Unclear metabolic mechanism (DME-unclear) DME1431 Holdemanella biformis Not Available Not Available [9]
Unclear metabolic mechanism (DME-unclear) DME1456 Roseburia intestinalis Not Available Not Available [9]
⏷ Show the Full List of 21  DME(s)
References
1 Carvedilol was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Metabolism of carvedilol in dogs, rats, and mice Drug Metab Dispos. 1998 Oct;26(10):958-69.
3 Pharmacokinetic interactions study between carvedilol and some antidepressants in rat liver microsomes - a comparative study. Med Pharm Rep. 2019 Apr;92(2):158-164.
4 The role of CYP2C9 genetic polymorphism in carvedilol O-desmethylation in vitro. Eur J Drug Metab Pharmacokinet. 2016 Feb;41(1):79-86.
5 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.
6 In vitro identification of the human cytochrome P450 enzymes involved in the metabolism of R(+)- and S(-)-carvedilol. Drug Metab Dispos. 1997 Aug;25(8):970-7.
7 Role of cytochrome P450 2D6 genetic polymorphism in carvedilol hydroxylation in vitro. Drug Des Devel Ther. 2016 Jun 8;10:1909-16.
8 Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8.
9 Mapping human microbiome drug metabolism by gut bacteria and their genes. Nature. 2019 Jun;570(7762):462-467.

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