General Information of DFM (ID: F21524)
Name	Tramadol 50 mg tablet
Company	RemedyRepack
Active Pharmaceutical Ingredient (API)	Tramadol		API Info click to show the detail info of this API
	Anaesthesia		ICD-11: 8E22	Approved
Drug Inactive Ingredient (DIGs)
	DIG ID	DIG Info	DIG Name	DIG Functional Class
	E03SQI	DIG Info	Carmellose sodium	Disintegrant
	E00DHW	DIG Info	Lactose monohydrate	Binding agent ...
	E01UTP	DIG Info	Magnesium stearate	lubricant
	E0AQ3D	DIG Info	Polysorbate 20	Dispersing agent ...
	E05BSD	DIG Info	Titanium dioxide	Coating agent ...

Full List of Biological Targets of DIG (DBTs) Regulated by DIG(s) in This DFM
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
Interacting DIG	Polysorbate 20
Biological Activity	IC50 = 320 uM (tested by experiment)					[1]
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 (1) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Magnesium stearate
Biological Activity	Protein expression downregulation (tested by experiment)					[2]
Tested Species	Homo sapiens (Human)
UniProt ID	CP3A4_HUMAN
Experiment (2) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Carmellose sodium
Biological Activity	Protein expression upregulation (tested by experiment)					[2]
Tested Species	Homo sapiens (Human)
UniProt ID	CP3A4_HUMAN
Experiment (3) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Carmellose sodium
Biological Activity	Protein expression upregulation (tested by experiment)					[2]
Tested Species	Homo sapiens (Human)
UniProt ID	CP3A4_HUMAN
Experiment (4) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polysorbate 20
Biological Activity	EC50 = 363.7 uM (tested by experiment)					[3]
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
Interacting DIG	Polysorbate 20
Biological Activity	IC50 = 64.1 uM (tested by experiment)					[3]
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
Interacting DIG	Polysorbate 20
Biological Activity	EC50 = 228.4 uM (tested by experiment)					[3]
Tested Species	Homo sapiens (Human)
UniProt ID	CP2C9_HUMAN
DBT Name: Mephenytoin 4-hydroxylase (CYP2C19)				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
Interacting DIG	Polysorbate 20
Biological Activity	IC50 = 230 uM (tested by experiment)					[3]
Tested Species	Homo sapiens (Human)
UniProt ID	CP2CJ_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
Interacting DIG	Polysorbate 20
Biological Activity	IC50 = 84 uM (tested by experiment)					[3]
Tested Species	Homo sapiens (Human)
UniProt ID	CP3A5_HUMAN
Primary active transporter (PAT)
DBT Name: Multidrug resistance protein 1 (ABCB1)				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
Interacting DIG	Polysorbate 20
Biological Activity	IC50 = 0.25 mg.mL-1 (tested by experiment)					[4]
Tested Species	Homo sapiens (Human)
UniProt ID	MDR1_HUMAN ; MDR3_HUMAN ; ABCB5_HUMAN
Experiment (2) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polysorbate 20
Biological Activity	Inhibition ratio > 240 % (tested by experiment)					[5]
Tested Species	Homo sapiens (Human)
UniProt ID	MDR1_HUMAN ; MDR3_HUMAN ; ABCB5_HUMAN
DBT Name: Urate exporter (BCRP)				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
Interacting DIG	Polysorbate 20
Biological Activity	Inhibition ratio > 84 % (tested by experiment)					[6]
Tested Species	Homo sapiens (Human)
UniProt ID	ABCG2_HUMAN
Experiment (2) for Assessing the Biological Activity of the Studied DIG on This DBT
Interacting DIG	Polysorbate 20
Biological Activity	Inhibition ratio > 50 % (tested by experiment)					[5]
Tested Species	Homo sapiens (Human)
UniProt ID	ABCG2_HUMAN

References
1	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.
2	Effects of commonly used excipients on the expression of CYP3A4 in colon and liver cells. Pharm Res. 2010 Aug;27(8):1703-12.
3	Mediation of in vitro cytochrome p450 activity by common pharmaceutical excipients. Mol Pharm. 2013 Jul 1;10(7):2739-48.
4	Reversal of multidrug resistance by surfactants. Br J Cancer. 1992 Jul;66(1):62-8.
5	Effect of excipients on breast cancer resistance protein substrate uptake activity. J Control Release. 2007 Dec 4;124(1-2):1-5.
6	Characterization of the inhibition of breast cancer resistance protein-mediated efflux of mitoxantrone by pharmaceutical excipients. Int J Pharm. 2009 Mar 31;370(1-2):216-9.

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