Disease Information

General Information of the Disease (ID: DIS00112)

• Name: Hyperlipoproteinaemia
• ICD: ICD-11: 5C80

Type(s) of Resistant Mechanism of This Disease

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Drug

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

Rosuvastatin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Solute carrier family 21 member 6 (SLC21A6) [1]

• Sensitive Disease: Hyperlipidemia [ICD-11: 5C80.Z]
• Sensitive Drug: Rosuvastatin
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Hyperlipoproteinaemia [ICD-11: 5C80]
• The Specified Disease: Familial hypercholesterolemia
• The Studied Tissue: Whole blood
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.27E-01; Fold-change: -2.34E-02; Z-score: -1.02E+00
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Enasidenib (and its metabolite, AGI-16903) at clinically relevant concentrations has effects on multiple drug metabolic enzymes and transporters, including inhibition of P-gp, BCRP, OATP1B1, and OATP1B3 transporters. When a single dose of rosuvastatin was administered together with 28 days of dosing of enasidenib, the AUC0-30 and AUC0-inf of rosuvastatin increased by =249% and 244%, respectively; and the Cmax increased by 366%, when compared to the single dose of rosuvastatin administered alone.

Key Molecule: Solute carrier family 21 member 8 (SLC21A8) [1]

• Sensitive Disease: Hyperlipidemia [ICD-11: 5C80.Z]
• Sensitive Drug: Rosuvastatin
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Hyperlipoproteinaemia [ICD-11: 5C80]
• The Specified Disease: Familial hypercholesterolemia
• The Studied Tissue: Whole blood
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.65E-01; Fold-change: -3.04E-02; Z-score: -1.48E+00
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Enasidenib (and its metabolite, AGI-16903) at clinically relevant concentrations has effects on multiple drug metabolic enzymes and transporters, including inhibition of P-gp, BCRP, OATP1B1, and OATP1B3 transporters. When a single dose of rosuvastatin was administered together with 28 days of dosing of enasidenib, the AUC0-30 and AUC0-inf of rosuvastatin increased by =249% and 244%, respectively; and the Cmax increased by 366%, when compared to the single dose of rosuvastatin administered alone.

Key Molecule: ATP-binding cassette sub-family G2 (ABCG2) [1], [2]

• Sensitive Disease: Hyperlipidemia [ICD-11: 5C80.Z]
• Sensitive Drug: Rosuvastatin
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Hyperlipoproteinaemia [ICD-11: 5C80]
• The Specified Disease: Familial hypercholesterolemia
• The Studied Tissue: Whole blood
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.28E-08; Fold-change: -1.96E-01; Z-score: -6.59E+00
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: qPCR
• Mechanism Description: Enasidenib (and its metabolite, AGI-16903) at clinically relevant concentrations has effects on multiple drug metabolic enzymes and transporters, including inhibition of P-gp, BCRP, OATP1B1, and OATP1B3 transporters. When a single dose of rosuvastatin was administered together with 28 days of dosing of enasidenib, the AUC0-30 and AUC0-inf of rosuvastatin increased by =249% and 244%, respectively; and the Cmax increased by 366%, when compared to the single dose of rosuvastatin administered alone.

References

• Ref 1: Assessment of Transporter-Mediated Drug Interactions for Enasidenib Based on a Cocktail Study in Patients With Relapse or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome. J Clin Pharmacol. 2022 Apr;62(4):494-504. doi: 10.1002/jcph.1979. Epub 2021 Oct 27.
• Ref 2: Characterization of the Human Intestinal Drug Transport with Ussing Chamber System Incorporating Freshly Isolated Human Jejunum. Drug Metab Dispos. 2021 Jan;49(1):84-93. doi: 10.1124/dmd.120.000138. Epub 2020 Oct 21.