Details of the Drug Combination

General Information of Drug Combination (ID: DCPI6UX)

• Drug Combination Name: Etravirine + Darunavir
• Indication: HIV/AIDS; Status: Phase 1 [1]
• Component Drugs:
  Etravirine (DMGV8QU): Small molecular drug
  Darunavir (DMN3GCH): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Etravirine

Disease Entry	ICD 11	Status	REF
Human immunodeficiency virus-1 infection	1C62	Approved	[2]

Etravirine 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	Modulator	[5]

Etravirine Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 3 (ABCC3)	DTQ3ZHF	MRP3_HUMAN	Substrate	[6]

Etravirine Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[7]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[7]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[8]

Indication(s) of Darunavir

Disease Entry	ICD 11	Status	REF
Human immunodeficiency virus infection	1C62	Approved	[3]
Human immunodeficiency virus-1 infection	1C62	Phase 3	[4]

Darunavir Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human immunodeficiency virus Protease (HIV PR)	TT5FNQT	POL_HV1B1	Modulator	[9]

Darunavir Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[10]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[11]
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[12]

Darunavir Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[13]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Acute HIV Infection	DC8931X	N. A.	Phase 4	[14]
Human Immunodeficiency Virus (HIV)	DC5AHVN	N. A.	Phase 2	[15]
HIV Infections	DC7ZBPE	N. A.	Phase 1	[16]
HIV-1 Infection	DCV1JJ5	N. A.	Phase 1	[17]

References

• [1] ClinicalTrials.gov (NCT00855088) Study in Healthy Males to Measure Darunavir and Etravirine in Blood, Seminal Fluid, and Rectal Tissue
• [2] Emerging antiviral drugs. Expert Opin Emerg Drugs. 2008 Sep;13(3):393-416.
• [3] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
• [6] Interaction potential of etravirine with drug transporters assessed in vitro. Antimicrob Agents Chemother. 2011 Mar;55(3):1282-4.
• [7] Pharmacokinetic interactions between etravirine and non-antiretroviral drugs. Clin Pharmacokinet. 2011 Jan;50(1):25-39.
• [8] Biotransformation of the antiretroviral drug etravirine: metabolite identification, reaction phenotyping, and characterization of autoinduction of cytochrome P450-dependent metabolism. Drug Metab Dispos. 2012 Apr;40(4):803-14.
• [9] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [10] Impact of drug transporters on cellular resistance towards saquinavir and darunavir. J Antimicrob Chemother. 2010 Nov;65(11):2319-28.
• [11] Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81.
• [12] P-glycoprotein mediates efflux transport of darunavir in human intestinal Caco-2 and ABCB1 gene-transfected renal LLC-PK1 cell lines. Biol Pharm Bull. 2009 Sep;32(9):1588-93.
• [13] Drug interactions with new and investigational antiretrovirals. Clin Pharmacokinet. 2009;48(4):211-41.
• [14] ClinicalTrials.gov (NCT00855413) HIV Viremia and Persistence in Acutely HIV-Infected Patients Treated With Darunavir/Ritonavir and Etravirine
• [15] ClinicalTrials.gov (NCT01199939) A Study of the Once Daily Combination of Etravirine and Darunavir/Ritonavir As Dual Therapy in Early Treatment-Experienced Patients
• [16] ClinicalTrials.gov (NCT00977756) IMPAACT P1058A: Pharmacokinetic Effects of New Antiretroviral Drugs on Children, Adolescents and Young Adults
• [17] ClinicalTrials.gov (NCT01641367) A5288/MULTI-OCTAVE: Management Using Latest Technologies to Optimize Combination Therapy After Viral Failure