Research Article Details
| Article ID: | A22926 |
| PMID: | 24205731 |
| Source: | Nihon Rinsho |
| Title: | [An inhibitor of intestinal cholesterol transporter]. |
| Abstract: | Ezetimibe is a unique inhibitor of intestinal cholesterol absorption. Ezetimibe selectively inhibits intestinal cholesterol absorption by blocking Niemann-Pick C1-like 1 (NPCIL1). Ezetimibe accelerates VLDL and TG degradation. Therefore, ezetimibe ameliorates postprandial hyperlipidemia. Ezetimibe inhibited the progression of nonalcoholic fatty liver disease (NAFLD) by correcting insulin resistance and decreasing small dense LDL-C in human subjects. In clinical study, ezetimibe administration combined with statin failed to inhibit progression of IMT thickness in ENHANCE (Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression) study. In this study baseline IMT thickness (0.7 mm) of patients was within normal range. Therefore only two years observation was too short to demonstrate anti-atherogenic effects of ezetimibe. SEAS(Simvastatin and Ezetimibe in Aortic Stenosis) trial examined effects of combination therapy with ezetimibe and statin in patients with aortic stenosis. Combination therapy could not inhibit progression of aortic stenosis. However, events of ischemic heart disease, especially CABG were significantly decreased only in combination group. Statin was not reported to reduce CVD(cardiovascular disease) in moderate to severe CKD patients. In SHARP(Study of Heart and Renal Protection) study, patients with severe renal disease were allocated either for statin alone group or combination therapy group with statin and ezetimibe. Combination therapy significantly decreased non-hemorrhagic stroke by 25 % compared with statin alone group in severe CKD and HD(hemodialysis) patients. Ezetimibe has unique lipid lowering profile increasing HDL-C concomitant with decreasing LDL-C and TG. Ezetimibe should be initiated first in patients with insulin resistant metabolic syndrome. Ezetimibe should be combined with statin to reduce not only LDL-C but RLP-C(remnant like lipoprotein particle choletserol) in type IIb dyslipidemia. |
| DOI: |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I16 | 6713 | Cerebrovascular disease | An vascular disease that is characterized by dysfunction of the blood vessels supplying the brain. http://en.wikipedia.org/wiki/Cerebrovascular_disease, http://www.ncbi.nlm.nih.gov/books/NBK378/ | disease of anatomical entity/ cardiovascular system disease/ vascular disease/cerebrovascular disease | Details |
| I13 | 3146 | Lipid metabolism disorder | An inherited metabolic disorder that involves the creation and degradation of lipids. http://en.wikipedia.org/wiki/Lipid_metabolism | disease of metabolism/ inherited metabolic disorder | Details |
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| I07 | 1936 | Arteriosclerosis | Build-up of fatty material and calcium deposition in the arterial wall resulting in partial or complete occlusion of the arterial lumen.https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=ncit&code=C35768 | disease of anatomical entity/cardiovascular system disease/ vascular disease/ artery disease | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D248 | Obeticholic Acid | Chemical drug | DB05990 | NR1H4 activator; NR1H4 agonist; FXR agonist | Enhance lipid metabolism | Approval rejected | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D131 | Ezetimibe | Chemical drug | DB00973 | SOAT1 inhibitor; | Enhance lipid metabolism | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |