Details of the Drug Combination

General Information of Drug Combination (ID: DCVZ9OE)

• Drug Combination Name: Cobicistat + Voriconazole
• Indication: Human Immunodeficiency Virus Type 1 (HIV-1) Infection; Status: Phase 1 [1]
• Component Drugs:
  Cobicistat (DM6L4H2): Small molecular drug
  Voriconazole (DMAOL2S): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Cobicistat

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

Cobicistat Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A (CYP3A)	TTIJQ3O	NOUNIPROTAC	Modulator	[2]

Cobicistat Interacts with 4 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[5]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[6]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[7]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[7]

Indication(s) of Voriconazole

Disease Entry	ICD 11	Status	REF
Aspergillosis	1F20	Approved	[3]
Candidiasis	1F23	Approved	[3]
Fusariosis	N.A.	Approved	[3]
Invasive aspergillosis	1F20.0	Approved	[4]
Invasive candidiasis	1F23	Approved	[3]
Neuroaspergillosis	N.A.	Approved	[3]
Candidemia	1F23.3Y	Investigative	[3]
Esophageal candidiasis	N.A.	Investigative	[3]

Voriconazole Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Candida Cytochrome P450 51 (Candi ERG11)	TTTSOUD	CP51_CANAL	Modulator	[8]

Voriconazole Interacts with 4 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[9]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[10]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[10]
Prostaglandin G/H synthase 1 (COX-1)	DE073H6	PGH1_HUMAN	Metabolism	[11]

Voriconazole Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2C19 (CYP2C19)	OTFMJYYE	CP2CJ_HUMAN	Decreases Activity	[12]

References

• [1] ClinicalTrials.gov (NCT05458102) Drug-Drug Interaction Study of Vesatolimod in Adults With HIV-1 Who Have Very Low or Undetectable Virus Levels
• [2] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7535).
• [3] Voriconazole FDA Label
• [4] Disk diffusion test and E-test with enriched Mueller-Hinton agar for determining susceptibility of Candida species to voriconazole and fluconazole. J Microbiol Immunol Infect. 2009 Apr;42(2):148-53.
• [5] Drug interactions between hormonal contraceptives and antiretrovirals. AIDS. 2017 Apr 24;31(7):917-952.
• [6] Cobicistat versus ritonavir boosting and differences in the drug-drug interaction profiles with co-medications. J Antimicrob Chemother. 2016 Jul;71(7):1755-8.
• [7] Pharmacokinetics and pharmacodynamics of GS-9350: a novel pharmacokinetic enhancer without anti-HIV activity. Clin Pharmacol Ther. 2010 Mar;87(3):322-9.
• [8] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [9] Roles of CYP3A4 and CYP2C19 in methyl hydroxylated and N-oxidized metabolite formation from voriconazole, a new anti-fungal agent, in human liver microsomes. Biochem Pharmacol. 2007 Jun 15;73(12):2020-6.
• [10] Effect of voriconazole on the pharmacokinetics of diclofenac. Fundam Clin Pharmacol. 2007 Dec;21(6):651-6.
• [11] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [12] The novel azole R126638 is a selective inhibitor of ergosterol synthesis in Candida albicans, Trichophyton spp., and Microsporum canis. Antimicrob Agents Chemother. 2004 Sep;48(9):3272-8.