Drug Information

Drug (ID: DG00274) and It's Reported Resistant Information

Name	Midazolam
Synonyms	Dazolam; Dormicum; Midanium; Midazolamum; Midosed; Versed; Midazolam Base; Dormicum (TN); Hypnovel (TN); Midacum (TN); Midazolamum [INN-Latin]; Ro 21-3981; Versed (TN); Midazolam (JAN/INN); Midazolam [INN:BAN:JAN]; 4H-Imidazo[1,5-a][1,4]benzodiazepine, 8-chloro-6-(2-fluoro-phenyl)-1-methyl-, (Z)-2-butenedioate; 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-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5a][1,4]benzodiazepine hydrochloride; 8-Chloro-6-(O-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 Click to Show/Hide
Indication	In total 2 Indication(s) Mood/affect symptom [ICD-11: MB24] Approved [1] Epilepsy/seizure [ICD-11: 8A61-8A6Z] Phase 3 [1]
Structure
Target	Translocator protein (TSPO)	TSPO_HUMAN	[1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula	C18H13ClFN3
IsoSMILES	CC1=NC=C2N1C3=C(C=C(C=C3)Cl)C(=NC2)C4=CC=CC=C4F
InChI	1S/C18H13ClFN3/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
InChIKey	DDLIGBOFAVUZHB-UHFFFAOYSA-N
PubChem CID	4192
ChEBI ID	CHEBI:6931
TTD Drug ID	D0U6LM
VARIDT ID	DR00684
DrugBank ID	DB00683

Type(s) of Resistant Mechanism of This Drug

DISM: Drug Inactivation by Structure Modification

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-07: Sleep-wake disorders

Click to Show/Hide the Resistance Disease of This Class

Insomnia [ICD-11: 7A00]

Click to Show/Hide

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Drug Inactivation by Structure Modification (DISM)			Click to Show/Hide
Key Molecule: Cytochrome P450 family 3 subfamily A member1 (CYP3A4)				[1]
Sensitive Disease	Insomnia [ICD-11: 7A00.0]			Disease Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	CaCo2 cells	Colon	Homo sapiens (Human)	CVCL_0025
	IPS cells	Colon	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	qPCR
Experiment for Drug Resistance	Transcellular transport study assay
Mechanism Description	The extraction ratio of metabolism of midazolam (a substrate of CYP3A4) to 1-OH midazolam in hiPSC-IECs was 0.534 +/- 0.009 (%), and decreased to 0.322 +/- 0.009 (%) and 0.0821 +/- 0.0064 (%) in the presence of 0.5 and 10 uM ketoconazole (an inhibitor of CYP3A4), respectively. The extraction ratio in Caco-2 cells was 0.0623 +/- 0.0038 (%) and also decreased to 0.0404 +/- 0.0023 (%) and 0.0414 +/- 0.0032 (%) in the presence of 0.5 and 10 uM ketoconazole, respectively.

References

Ref 1	Application of Intestinal Epithelial Cells Differentiated from Human Induced Pluripotent Stem Cells for Studies of Prodrug Hydrolysis and Drug Absorption in the Small Intestine. Drug Metab Dispos. 2018 Nov;46(11):1497-1506. doi: 10.1124/dmd.118.083246. Epub 2018 Aug 22.