Details of the Drug Combination

General Information of Drug Combination (ID: DCOWAAF)

• Drug Combination Name: Tenofovir + Rilpivirine
• Indication: AIDS; Status: Phase 1 [1]
• Component Drugs:
  Tenofovir (DM1IS6U): Small molecular drug
  Rilpivirine (DMJ0QOW): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Tenofovir

Disease Entry	ICD 11	Status	REF
Chronic hepatitis B virus infection	N.A.	Approved	[2]
Hepatitis B virus infection	1E51.0	Approved	[2]
Human immunodeficiency virus infection	1C62	Approved	[3]

Tenofovir Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human immunodeficiency virus Reverse transcriptase (HIV RT)	TT84ETX	POL_HV1B1	Inhibitor	[6]

Tenofovir Interacts with 7 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[7]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[8]
Multidrug resistance-associated protein 4 (ABCC4)	DTCSGPB	MRP4_HUMAN	Substrate	[9]
Organic anion transporter 1 (SLC22A6)	DTQ23VB	S22A6_HUMAN	Substrate	[10]
Organic anion transporter 3 (SLC22A8)	DTVP67E	S22A8_HUMAN	Substrate	[11]
Multidrug resistance-associated protein 7 (ABCC10)	DTPS120	MRP7_HUMAN	Substrate	[12]
Multidrug resistance-associated protein 8 (ABCC11)	DTWN7FC	ABCCB_HUMAN	Substrate	[13]

Indication(s) of Rilpivirine

Disease Entry	ICD 11	Status	REF
Human immunodeficiency virus infection	1C62	Approved	[4]
Pain	MG30-MG3Z	Investigative	[5]

Rilpivirine Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human immunodeficiency virus Reverse transcriptase (HIV RT)	TT84ETX	POL_HV1B1	Inhibitor	[14]
Voltage-gated sodium channel alpha Nav1.8 (SCN10A)	TT90XZ8	SCNAA_HUMAN	Inhibitor	[5]

Rilpivirine Interacts with 4 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[15]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[16]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[17]
UDP-glucuronosyltransferase 1A4 (UGT1A4)	DELOY3P	UD14_HUMAN	Metabolism	[16]

References

• [1] ClinicalTrials.gov (NCT03782142) Effect on HIV Medications on EPC Cells
• [2] Tenofovir FDA Label
• [3] Anti-hepatitis B virus activity in vitro of combinations of tenofovir with nucleoside/nucleotide analogues. Antivir Chem Chemother. 2009;19(4):165-76.
• [4] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [5] Structures of muO-conotoxins from Conus marmoreus. I nhibitors of tetrodotoxin (TTX)-sensitive and TTX-resistant sodium channels in mammalian senso... J Biol Chem. 2004 Jun 11;279(24):25774-82.
• [6] Antiviral drugs in current clinical use. J Clin Virol. 2004 Jun;30(2):115-33.
• [7] KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01665)
• [8] KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01913)
• [9] Functional involvement of multidrug resistance-associated protein 4 (MRP4/ABCC4) in the renal elimination of the antiviral drugs adefovir and tenofovir. Mol Pharmacol. 2007 Feb;71(2):619-27.
• [10] Human renal organic anion transporter 1 (hOAT1) and its role in the nephrotoxicity of antiviral nucleotide analogs. Nucleosides Nucleotides Nucleic Acids. 2001 Apr-Jul;20(4-7):641-8.
• [11] Tenofovir alafenamide is not a substrate for renal organic anion transporters (OATs) and does not exhibit OAT-dependent cytotoxicity. Antivir Ther. 2014;19(7):687-92.
• [12] Genetic variants of ABCC10, a novel tenofovir transporter, are associated with kidney tubular dysfunction. J Infect Dis. 2011 Jul 1;204(1):145-53.
• [13] Tenofovir Disoproxil Fumarate Is a New Substrate of ATP-Binding Cassette Subfamily C Member 11. Antimicrob Agents Chemother. 2017 Mar 24;61(4). pii: e01725-16.
• [14] Emerging antiviral drugs. Expert Opin Emerg Drugs. 2008 Sep;13(3):393-416.
• [15] Potential of the novel antiretroviral drug rilpivirine to modulate the expression and function of drug transporters and drug-metabolising enzymes in vitro. Int J Antimicrob Agents. 2013 May;41(5):484-7.
• [16] Human biotransformation of the nonnucleoside reverse transcriptase inhibitor rilpivirine and a cross-species metabolism comparison. Antimicrob Agents Chemother. 2013 Oct;57(10):5067-79.
• [17] Population pharmacokinetics and pharmacogenetics analysis of rilpivirine in HIV-1-infected individuals. Antimicrob Agents Chemother. 2016 Dec 27;61(1).