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

General Information of Drug (ID: DR0509)
Drug Name
Diltiazem hydrochloride
Synonyms
Dilicardin; Dilpral; Diltahexal; Diltelan; Diltiasyn; Diltiazem HCl; Diltiazem hydrochloride; Diltikor; Diltime; Dilzem; Dilzene; Dilzicardin; Dinisor; Dodexen; Farmabes; Gadoserin; Helsibon; Herbesser; Incoril; Kaltiazen; Lacerol; Levozem; Longazem; Lytelsen; Masdil; Miocardie; Mono-Tildiem; Oxycardil; Poltiazem; Presoken; Surazem; Tilazem; Tildiem; Trumsal; Ziruvate; Diltiazem; Diltiazem [INN:BAN]; Diltiazemum; Diltiazemum [INN-Latin]; Diltiazen; Dilticard; Diltzac; Dilzen; EE92BBP03H; EINECS 255-796-4; Endrydil; HSDB 6528; HSUGRBWQSSZJOP-RTWAWAEBSA-N; Incoril AP; Tiamate; Tiazac XC; UNII-EE92BBP03H; d-cis-Diltiazem; (+)-cis-diltiazem; (+)-diltiazem; 42399-41-7; Acalix; Adizem; Anoheal; BRN 3573079; CHEBI:101278; CHEMBL23; Cardil; Cardizem; Dilacor; Dilacor-XR; Dilcontin; Dilren; Dilt-cd; Dilta-Hexal; (+)-cis-Diltiazem hydrochloride; 33286-22-5; Altiazem; Anginyl; Bi-Tildiem; Britiazim; CRD-401; Calnurs; Cardizem CD; Cardizem LA; Cirilen; Citizen; Clarute; Corazet; Deltazen
Indication Essential hypertension [ICD11: BA00] Approved [1]
Structure
3D MOL is unavailable 2D MOL
Pharmaceutical Properties Molecular Weight 451 Topological Polar Surface Area 84.4
Heavy Atom Count 30 Rotatable Bond Count 7
Hydrogen Bond Donor Count 1 Hydrogen Bond Acceptor Count 6
Cross-matching ID
PubChem CID
62920
ChEBI ID
CHEBI:645509
CAS Number
33286-22-5
TTD Drug ID
D0OB1J
Formula
C22H27ClN2O4S
Canonical SMILES
CC(=O)OC1C(SC2=CC=CC=C2N(C1=O)CCN(C)C)C3=CC=C(C=C3)OC.Cl
InChI
1S/C22H26N2O4S.ClH/c1-15(25)28-20-21(16-9-11-17(27-4)12-10-16)29-19-8-6-5-7-18(19)24(22(20)26)14-13-23(2)3;/h5-12,20-21H,13-14H2,1-4H3;1H/t20-,21+;/m1./s1
InChIKey
HDRXZJPWHTXQRI-BHDTVMLSSA-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
Deacetyl diltiazem DM000101 N. A. Oxidation - Deacetylation 1 [9]
N-monodesmethyl diltilazem DM000097 N. A. Oxidation - N-Demethylation 1 [9]
O-desmethyl diltiazem DM000104
71433758
Oxidation - O-Demethylation 1 [9]
Deacetyl diltiazem N-oxide DM000103
71315210
Oxidation - N-Oxidation 2 [10]
Deacetyl N-monodesmethyl diltiazem DM000098 N. A. Conjugation - Acetylation 2 [10]
Deacetyl O-desmethyl diltiazem DM000102
10021324
Oxidation - O-Demethylation 2 [10] , [9]
N,O-didesmethyl diltiazem DM000100 N. A. Oxidation - O-Demethylation 2 [10] , [9]
Deacetyl N,O-didesmethyl diltiazem DM000099
10472681
Oxidation - O-Demethylation 3 [9]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR000868 Diltiazem hydrochloride N-monodesmethyl diltilazem Oxidation - N-Demethylation CYP3A4 [9]
MR000869 Diltiazem hydrochloride Deacetyl diltiazem Oxidation - Deacetylation LE [9]
MR000870 Diltiazem hydrochloride O-desmethyl diltiazem Oxidation - O-Demethylation CYP2D6 [9]
MR000866 Deacetyl diltiazem Deacetyl O-desmethyl diltiazem Oxidation - O-Demethylation CYP2D6 [10], [9]
MR000867 Deacetyl diltiazem Deacetyl diltiazem N-oxide Oxidation - N-Oxidation Unclear [10]
MR000863 N-monodesmethyl diltilazem Deacetyl N-monodesmethyl diltiazem Conjugation - Acetylation LE [10]
MR000864 N-monodesmethyl diltilazem N,O-didesmethyl diltiazem Oxidation - O-Demethylation CYP2D6 [10], [9]
MR000865 Deacetyl N-monodesmethyl diltiazem Deacetyl N,O-didesmethyl diltiazem Oxidation - O-Demethylation CYP2D6 [9]
⏷ Show the Full List of 8 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cytochrome P450 2C8 (CYP2C8) DME0018 Homo sapiens
CP2C8_HUMAN
1.14.14.1
[2]
Cytochrome P450 2C9 (CYP2C9) DME0019 Homo sapiens
CP2C9_HUMAN
1.14.14.1
[3]
Cytochrome P450 2D6 (CYP2D6) DME0009 Homo sapiens
CP2D6_HUMAN
1.14.14.1
[3]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[4]
Cytochrome P450 3A5 (CYP3A5) DME0012 Homo sapiens
CP3A5_HUMAN
1.14.14.1
[5]
Cytochrome P450 3A7 (CYP3A7) DME0015 Homo sapiens
CP3A7_HUMAN
1.14.14.1
[6]
Mephenytoin 4-hydroxylase (CYP2C19) DME0021 Homo sapiens
CP2CJ_HUMAN
1.14.14.1
[7]
Unclear metabolic mechanism (DME-unclear) DME1254 Bacteroides thetaiotaomicron Not Available Not Available [8]
Unclear metabolic mechanism (DME-unclear) DME1256 Bacteroides sartorii Not Available Not Available [8]
Unclear metabolic mechanism (DME-unclear) DME1357 Alistipes indistinctus Not Available Not Available [8]
Unclear metabolic mechanism (DME-unclear) DME1365 Bacteroides dorei Not Available Not Available [8]
Unclear metabolic mechanism (DME-unclear) DME1376 Bacteroides ovatus Not Available Not Available [8]
Unclear metabolic mechanism (DME-unclear) DME1385 Bacteroides xylanisolvens Not Available Not Available [8]
Unclear metabolic mechanism (DME-unclear) DME1393 Blautia hansenii Not Available Not Available [8]
Unclear metabolic mechanism (DME-unclear) DME1402 Clostridium botulinum Not Available Not Available [8]
Unclear metabolic mechanism (DME-unclear) DME1445 Parabacteroides distasonis Not Available Not Available [8]
Unclear metabolic mechanism (DME-unclear) DME1446 Parabacteroides johnsonii Not Available Not Available [8]
Unclear metabolic mechanism (DME-unclear) DME1470 Victivallis vadensis Not Available Not Available [8]
⏷ Show the Full List of 18  DME(s)
References
1 Diltiazem Hydrochloride was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Role of CYP3A4 in human hepatic diltiazem N-demethylation: inhibition of CYP3A4 activity by oxidized diltiazem metabolites. J Pharmacol Exp Ther. 1997 Jul;282(1):294-300.
3 Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metab Dispos. 2000 Feb;28(2):125-30.
4 Comparative metabolic capabilities of CYP3A4, CYP3A5, and CYP3A7. Drug Metab Dispos. 2002 Aug;30(8):883-91.
5 Significant impacts of CYP3A4*1G and CYP3A5*3 genetic polymorphisms on the pharmacokinetics of diltiazem and its main metabolites in Chinese adult kidney transplant patients. J Clin Pharm Ther. 2016 Jun;41(3):341-7.
6 FDA Drug Development and Drug Interactions
7 Effects of CYP3A4 inhibition by diltiazem on pharmacokinetics and dynamics of diazepam in relation to CYP2C19 genotype status. Drug Metab Dispos. 2001 Oct;29(10):1284-9.
8 Mapping human microbiome drug metabolism by gut bacteria and their genes. Nature. 2019 Jun;570(7762):462-467.
9 Desacetyl-diltiazem displays severalfold higher affinity to CYP2D6 compared with CYP3A4. Drug Metab Dispos. 2002 Jan;30(1):1-3.
10 Pharmacokinetics and metabolism of diltiazem in healthy males and females following a single oral dose Eur J Drug Metab Pharmacokinet. 1993 Apr-Jun;18(2):199-206. doi: 10.1007/BF03188796.

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