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

General Information of Drug (ID: DR1086)
Drug Name
Midazolam hydrochloride
Synonyms
Midazolam Base; Midazolamum; Midazolamum [INN-Latin]; Midazolam Hcl; Midazolam hydrochloride (USAN); Midazolam hydrochloride [USAN]; Ro 21-3981/001; Ro 21-3981/003; W7TTW573JJ; 59467-96-8; 8-Chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo(1,5-a)(1,4)benzodiazepine hydrochloride; 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4]benzodiazepine hydrochloride; DSSTox_CID_27824; DSSTox_GSID_47846; DSSTox_RID_82587; EINECS 261-776-6; HSDB 6751; Rocam; UNII-W7TTW573JJ; Hypnovel; MIDAZOLAM HYDROCHLORIDE; R60L0SM5BC; Ro 21-3981; mezolam; midazolam; 59467-70-8; 8-Chlor-6-(2-fluorphenyl)-1-methyl-4H-imidazo(1,5-a)(1,4)benzodiazepin; 8-Chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4]benzodiazepine; 8-Chloro-6-(o-fluorophenyl)-1-methyl-4H-imidazo(1,5-a)(1,4)benzodiazepine; BRN 0625572; C18H13ClFN3; CHEBI:6931; CHEMBL655; DEA No. 2884; EINECS 261-774-5; UNII-R60L0SM5BC; Buccolam; DDLIGBOFAVUZHB-UHFFFAOYSA-N
Indication Anxiety disorder [ICD11: 6B00] Approved [1]
Structure
3D MOL is unavailable 2D MOL
Pharmaceutical Properties Molecular Weight 362.2 Topological Polar Surface Area 30.2
Heavy Atom Count 24 Rotatable Bond Count 1
Hydrogen Bond Donor Count 1 Hydrogen Bond Acceptor Count 3
Cross-matching ID
PubChem CID
43032
ChEBI ID
CHEBI:6932
CAS Number
59467-96-8
TTD Drug ID
D0U6LM
Formula
C18H14Cl2FN3
Canonical SMILES
CC1=NC=C2N1C3=C(C=C(C=C3)Cl)C(=NC2)C4=CC=CC=C4F.Cl
InChI
1S/C18H13ClFN3.ClH/c1-11-21-9-13-10-22-18(14-4-2-3-5-16(14)20)15-8-12(19)6-7-17(15)23(11)13;/h2-9H,10H2,1H3;1H
InChIKey
PLYSCVSCYOQVRP-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',4'-dihydroxymidazolam DM004421
10316307
Unclear 1 [9]
1-hydroxymidazolam glucuronide DM004419
133640
Conjugation - N-glucuronidation 1 [6] , [7] , [8]
4-hydroxymidazolam DM004416
124449
Oxidation - 4-hydroxylation 1 [10]
4-hydroxymidazolam glucuronide DM004420
71777598
Conjugation - N-glucuronidation 1 [6] , [7]
Alpha-hydroxymidazolam DM004418
107917
Oxidation - 1'-hydroxylation 1 [10] , [8]
1',4'-dihydroxymidazolam DM004421
10316307
Unclear 2 [9]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR004742 Midazolam hydrochloride 4-hydroxymidazolam Oxidation - 4-hydroxylation CYP3A4 [10]
MR004744 Midazolam hydrochloride Alpha-hydroxymidazolam Oxidation - 1'-hydroxylation CYP3A4 [10], [8]
MR004745 Midazolam hydrochloride 1-hydroxymidazolam glucuronide Conjugation - N-glucuronidation UGT1A4 ... [6], [7], [8]
MR004746 Midazolam hydrochloride 4-hydroxymidazolam glucuronide Conjugation - N-glucuronidation UGT1A4 ... [6], [7]
MR004747 Midazolam hydrochloride 1',4'-dihydroxymidazolam Unclear Unclear [9]
MR004743 4-hydroxymidazolam 1',4'-dihydroxymidazolam Unclear Unclear [9]
⏷ Show the Full List of 6 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cytochrome P450 2B6 (CYP2B6) DME0020 Homo sapiens
CP2B6_HUMAN
1.14.14.1
[2]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[3]
Cytochrome P450 3A5 (CYP3A5) DME0012 Homo sapiens
CP3A5_HUMAN
1.14.14.1
[4]
Cytochrome P450 3A7 (CYP3A7) DME0015 Homo sapiens
CP3A7_HUMAN
1.14.14.1
[5]
Cytochrome P450 4B1 (CYP4B1) DME0010 Homo sapiens
CP4B1_HUMAN
1.14.14.1
[5]
UDP-glucuronosyltransferase 1A4 (UGT1A4) DME0048 Homo sapiens
UD14_HUMAN
2.4.1.17
[6] , [7] , [8]
UDP-glucuronosyltransferase 2B4 (UGT2B4) DME0047 Homo sapiens
UD2B4_HUMAN
2.4.1.17
[6] , [7] , [8]
UDP-glucuronosyltransferase 2B7 (UGT2B7) DME0040 Homo sapiens
UD2B7_HUMAN
2.4.1.17
[6] , [7] , [8]
⏷ Show the Full List of 8  DME(s)
References
1 Midazolam Hydrochloride was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Further characterization of the expression in liver and catalytic activity of CYP2B6. J Pharmacol Exp Ther. 1998 Sep;286(3):1253-9.
3 Selection of alternative CYP3A4 probe substrates for clinical drug interaction studies using in vitro data and in vivo simulation. Drug Metab Dispos. 2010 Jun;38(6):981-7.
4 In vitro metabolism of midazolam, triazolam, nifedipine, and testosterone by human liver microsomes and recombinant cytochromes p450: role of cyp3a4 and cyp3a5. Drug Metab Dispos. 2003 Jul;31(7):938-44.
5 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
6 The inhibition study of human UDP-glucuronosyltransferases with cytochrome P450 selective substrates and inhibitors
7 Contribution of the N-glucuronidation pathway to the overall in vitro metabolic clearance of midazolam in humans
8 The Oral Bioavailability and Metabolism of Midazolam in Stable Critically Ill Children: A Pharmacokinetic Microtracing Study
9 Pharmacokinetics and metabolism of midazolam in chimeric mice with humanised livers
10 Heterotropic activation of the midazolam hydroxylase activity of CYP3A by a positive allosteric modulator of mGlu5: in vitro to in vivo translation and potential impact on clinically relevant drug-drug interactions

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