Details of the Drug Combination

General Information of Drug Combination (ID: DC8YKF6)

• Drug Combination Name: Voriconazole + Caspofungin
• Indication: Infection; Status: Phase 1 [1]
• Component Drugs:
  Voriconazole (DMAOL2S): Small molecular drug
  Caspofungin (DMGQIPT): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Voriconazole

Disease Entry	ICD 11	Status	REF
Aspergillosis	1F20	Approved	[2]
Candidiasis	1F23	Approved	[2]
Fusariosis	N.A.	Approved	[2]
Invasive aspergillosis	1F20.0	Approved	[3]
Invasive candidiasis	1F23	Approved	[2]
Neuroaspergillosis	N.A.	Approved	[2]
Candidemia	1F23.3Y	Investigative	[2]
Esophageal candidiasis	N.A.	Investigative	[2]

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	[6]

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	[7]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[8]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[8]
Prostaglandin G/H synthase 1 (COX-1)	DE073H6	PGH1_HUMAN	Metabolism	[9]

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	[10]

Indication(s) of Caspofungin

Disease Entry	ICD 11	Status	REF
Candidiasis	1F23	Approved	[4]
Fungal infection	1F29-1F2F	Approved	[5]
Mycoses	1F2Z	Approved	[4]
Mycosis fungoides	2B01	Approved	[4]
Candidemia	1F23.3Y	Investigative	[4]
Esophageal candidiasis	N.A.	Investigative	[4]

Caspofungin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Fungal 1,3-beta-glucan synthase (Fung GSC2)	TT0SFXH	FKS2_YEAST	Modulator	[6]

Caspofungin Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[11]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Candidiasis, Invasive	DCER6ES	N. A.	Phase 1	[12]

References

• [1] ClinicalTrials.gov (NCT00238355) Voriconazole and Caspofungin Acetate in Treating Invasive Fungal Infections in Patients With Weakened Immune Systems
• [2] Voriconazole FDA Label
• [3] 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.
• [4] Caspofungin FDA Label
• [5] Echinocandins: pharmacokinetic and therapeutic issues. Curr Med Res Opin. 2009 Jul;25(7):1741-50.
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [7] 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.
• [8] Effect of voriconazole on the pharmacokinetics of diclofenac. Fundam Clin Pharmacol. 2007 Dec;21(6):651-6.
• [9] 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.
• [10] 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.
• [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] ClinicalTrials.gov (NCT00413218) Isavuconazole (BAL8557) in the Treatment of Candidemia and Other Invasive Candida Infections