Disease Information

General Information of the Disease (ID: DIS00007)

• Name: Insomnia
• ICD: ICD-11: 7A00

Type(s) of Resistant Mechanism of This Disease

  DISM: Drug Inactivation by Structure Modification

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Midazolam

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Cytochrome P450 family 3 subfamily A member1 (CYP3A4) [1]

• Sensitive Disease: Insomnia [ICD-11: 7A00.0]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Midazolam
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: CaCo2 cells; Colon; Homo sapiens (Human); CVCL_0025
• In Vitro Model: 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.