General Information of DIG (ID: E09KOV)
DIG Name	Poloxamer 188
DIG Function	Emulsifying agent; Solubilizing agent; Surfactant

Full List of Active Pharmaceutical Ingredients (APIs) Co-administrated with This DIG
ICD Disease Classification 01			Infectious/parasitic disease		Click to Show/Hide
Itraconazole		API Info	Blastomycosis [ICD-11: 1F22]			[1]
Griseofulvin		API Info	Dermatophytosis [ICD-11: 1F28]			[2]
Mefloquine		API Info	Malaria [ICD-11: 1F40]			[3]
ICD Disease Classification 02			Benign/in-situ/malignant neoplasm		Click to Show/Hide
Bosutinib		API Info	Chronic myelogenous leukaemia [ICD-11: 2A20]			[4]
Nilotinib		API Info	Chronic myelogenous leukaemia [ICD-11: 2A20]			[5]
ICD Disease Classification 05			Endocrine/nutritional/metabolic disease		Click to Show/Hide
Fenofibrate		API Info	Hypertriglyceridaemia [ICD-11: 5C80]			[6]
Glimepiride		API Info	Diabetes mellitus [ICD-11: 5A10]			[7]
Lovastatin		API Info	Hypertriglyceridaemia [ICD-11: 5C80]			[8]
Repaglinide		API Info	Diabetes mellitus [ICD-11: 5A10]			[9]
Deferasirox		API Info	Hyperphosphatemia [ICD-11: 5C64]			[10]
ICD Disease Classification 06			Mental/behavioural/neurodevelopmental disorder		Click to Show/Hide
Alprazolam		API Info	Anxiety disorder [ICD-11: 6B00]			[11]
Disulfiram		API Info	Alcohol dependence [ICD-11: 6C40]			[12]
ICD Disease Classification 08			Nervous system disease		Click to Show/Hide
Carbamazepine		API Info	Epilepsy [ICD-11: 8A60]			[13]
ICD Disease Classification 11			Circulatory system disease		Click to Show/Hide
Metoprolol		API Info	Essential hypertension [ICD-11: BA00]			[14]
Valsartan		API Info	Essential hypertension [ICD-11: BA00]			[15]
Irbesartan		API Info	Essential hypertension [ICD-11: BA00]			[16]
ICD Disease Classification 12			Respiratory system disease		Click to Show/Hide
Sirolimus		API Info	Lymphangioleiomyomatosis [ICD-11: CB07]			[17]
ICD Disease Classification 13			Digestive system disease		Click to Show/Hide
Esomeprazole		API Info	Duodenal ulcer [ICD-11: DA63]			[18]
Tacrolimus		API Info	Ulcerative colitis [ICD-11: DD71]			[19]
ICD Disease Classification 14			Skin disease		Click to Show/Hide
Acitretin		API Info	Psoriasis vulgaris [ICD-11: EA90]			[20]
ICD Disease Classification 15			Musculoskeletal/connective-tissue disease		Click to Show/Hide
Prednisone		API Info	Rheumatoid arthritis [ICD-11: FA20]			[21]

Full List of Biological Targets of DIG (DBTs) Regulated by This DIG
Oxidoreductase (ORase)
DBT Name: Cytochrome P450 3A (CYP3A)			Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment for Assessing the Biological Activity of the Studied DIG on This DBT
Biological Activity	IC50 = 750 uM (tested by experiment)				[22]
Tested Species	Homo sapiens (Human)
UniProt ID	CP3A4_HUMAN ; CP3A5_HUMAN ; CP3A7_HUMAN ; CP343_HUMAN
DBT Name: Albendazole monooxygenase (CYP3A4)			Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment for Assessing the Biological Activity of the Studied DIG on This DBT
Biological Activity	IC50 = 60 uM (tested by experiment)				[23]
Tested Species	Homo sapiens (Human)
UniProt ID	CP3A4_HUMAN
DBT Name: Cytochrome P450 2E1 (CYP2E1)			Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment for Assessing the Biological Activity of the Studied DIG on This DBT
Biological Activity	IC50 = 203.7 uM (tested by experiment)				[23]
Tested Species	Homo sapiens (Human)
UniProt ID	CP2E1_HUMAN
DBT Name: Cytochrome P450 2C9 (CYP2C9)			Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment for Assessing the Biological Activity of the Studied DIG on This DBT
Biological Activity	IC50 = 244.8 uM (tested by experiment)				[23]
Tested Species	Homo sapiens (Human)
UniProt ID	CP2C9_HUMAN
DBT Name: Debrisoquine 4-hydroxylase (CYP2D6)			Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment for Assessing the Biological Activity of the Studied DIG on This DBT
Biological Activity	EC50 = 387.6 uM (tested by experiment)				[23]
Tested Species	Homo sapiens (Human)
UniProt ID	CP2D6_HUMAN
DBT Name: Cytochrome P450 3A5 (CYP3A5)			Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment for Assessing the Biological Activity of the Studied DIG on This DBT
Biological Activity	IC50 = 210 uM (tested by experiment)				[23]
Tested Species	Homo sapiens (Human)
UniProt ID	CP3A5_HUMAN
Primary active transporter (PAT)
DBT Name: Multidrug resistance protein 2 (ABCC2)			Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment (1) for Assessing the Biological Activity of the Studied DIG on This DBT
Biological Activity	Inhibition ratio = 53 % (tested by experiment)				[24]
Tested Species	Homo sapiens (Human)
UniProt ID	MRP2_HUMAN
Experiment (2) for Assessing the Biological Activity of the Studied DIG on This DBT
Biological Activity	Inhibition ratio > 55 % (tested by experiment)				[25]
Tested Species	Homo sapiens (Human)
UniProt ID	MRP2_HUMAN
Cell line (CELL)
DBT Name: Colon cancer Caco-2 cells (Caco-2)			Click to Show/Hide
Detailed Information	DBT Info click to show the detail info of this DBT
Experiment for Assessing the Biological Activity of the Studied DIG on This DBT
Biological Activity	Chylomicron secretion downregulation (tested by experiment)				[26]
Tested Species	Homo sapiens (Human)

References
1	FDA label for approved itraconazole from the official website of the U.S. Food and Drug Administration.
2	FDA label for approved griseofulvin from the official website of the U.S. Food and Drug Administration.
3	FDA label for approved mefloquine from the official website of the U.S. Food and Drug Administration.
4	FDA label for approved bosutinib from the official website of the U.S. Food and Drug Administration.
5	FDA label for approved nilotinib from the official website of the U.S. Food and Drug Administration.
6	FDA label for approved fenofibrate from the official website of the U.S. Food and Drug Administration.
7	FDA label for approved glimepiride from the official website of the U.S. Food and Drug Administration.
8	FDA label for approved lovastatin from the official website of the U.S. Food and Drug Administration.
9	FDA label for approved repaglinide from the official website of the U.S. Food and Drug Administration.
10	FDA label for approved deferasirox from the official website of the U.S. Food and Drug Administration.
11	FDA label for approved alprazolam from the official website of the U.S. Food and Drug Administration.
12	FDA label for approved disulfiram from the official website of the U.S. Food and Drug Administration.
13	FDA label for approved carbamazepine from the official website of the U.S. Food and Drug Administration.
14	FDA label for approved metoprolol from the official website of the U.S. Food and Drug Administration.
15	FDA label for approved valsartan from the official website of the U.S. Food and Drug Administration.
16	FDA label for approved irbesartan from the official website of the U.S. Food and Drug Administration.
17	FDA label for approved sirolimus from the official website of the U.S. Food and Drug Administration.
18	FDA label for approved esomeprazole from the official website of the U.S. Food and Drug Administration.
19	FDA label for approved tacrolimus from the official website of the U.S. Food and Drug Administration.
20	FDA label for approved acitretin from the official website of the U.S. Food and Drug Administration.
21	FDA label for approved prednisone from the official website of the U.S. Food and Drug Administration.
22	Nonionic surfactants are strong inhibitors of cytochrome P450 3A biotransformation activity in vitro and in vivo. Eur J Pharm Sci. 2009 Mar 2;36(4-5):401-11.
23	Mediation of in vitro cytochrome p450 activity by common pharmaceutical excipients. Mol Pharm. 2013 Jul 1;10(7):2739-48.
24	Inhibition of human efflux transporter ABCC2 (MRP2) by self-emulsifying drug delivery system: influences of concentration and combination of excipients. J Pharm Pharm Sci. 2014;17(4):447-60.
25	Interactions between human multidrug resistance related protein (MRP2; ABCC2) and excipients commonly used in self-emulsifying drug delivery systems (SEDDS). Int J Pharm. 2013 Apr 15;447(1-2):192-8.
26	The effects of pluronics block copolymers and Cremophor EL on intestinal lipoprotein processing and the potential link with P-glycoprotein in Caco-2 cells. Pharm Res. 2003 Jul;20(7):1085-92.

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