CIDOFOVIR SODIUM

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C8H12N3O6P.2Na
Molecular Weight	323.1507
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Na+].[Na+].NC1=NC(=O)N(C[C@@H](CO)OCP([O-])([O-])=O)C=C1

InChI

InChIKey=HKIAHFPOQYDOHP-ILKKLZGPSA-L

InChI=1S/C8H14N3O6P.2Na/c9-7-1-2-11(8(13)10-7)3-6(4-12)17-5-18(14,15)16;;/h1-2,6,12H,3-5H2,(H2,9,10,13)(H2,14,15,16);;/q;2*+1/p-2/t6-;;/m0../s1

HIDE SMILES / InChI

Molecular Formula	C8H12N3O6P
Molecular Weight	277.1711
Charge	-2
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	Na
Molecular Weight	22.9898
Charge	1
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.gilead.com/~/media/files/pdfs/medicines/other/vistide/vistide.pdf
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/10473024 | https://www.ncbi.nlm.nih.gov/pubmed/8630098

Cidofovir is an antiviral nucleotide analogue with significant activity against cytomegalovirus (CMV) and other herpesviruses. Cidofovir suppresses cytomegalovirus (CMV) replication by selective inhibition of viral DNA synthesis. Biochemical data support selective inhibition of CMV DNA polymerase by cidofovir diphosphate, the active intracellular metabolite of cidofovir. Incorporation of cidofovir into the growing viral DNA chain results in reductions in the rate of viral DNA synthesis. Cidofovir is indicated for the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Human herpesvirus 5 DNA polymerase 17 Target ID: CHEMBL3414 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8630098	Inhibitor 8146

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cytomegalovirus retinitis 15 Sources: http://www.gilead.com/~/media/files/pdfs/medicines/other/vistide/vistide.pdf	Primary		Approved 8307	VISTIDE Approved Use Cidofovir injection is indicated for the treatment of cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome (AIDS). Launch Date 8.3574718E11

C_max

Value	Dose	Analyte	Population
7.34 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7574510	3 mg/kg 1 times / week other, intravenous dose: 3 mg/kg route of administration: Intravenous experiment type: OTHER co-administered:	CIDOFOVIR serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
11.5 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7574510	5 mg/kg 1 times / week other, intravenous dose: 5 mg/kg route of administration: Intravenous experiment type: OTHER co-administered:	CIDOFOVIR serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3.12 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7574510	1 mg/kg 1 times / week other, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: OTHER co-administered:	CIDOFOVIR serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
19.96 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7574510	3 mg/kg 1 times / week other, intravenous dose: 3 mg/kg route of administration: Intravenous experiment type: OTHER co-administered:	CIDOFOVIR serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
28.34 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7574510	5 mg/kg 1 times / week other, intravenous dose: 5 mg/kg route of administration: Intravenous experiment type: OTHER co-administered:	CIDOFOVIR serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
8.35 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7574510	1 mg/kg 1 times / week other, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: OTHER co-administered:	CIDOFOVIR serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
2.72 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7574510	3 mg/kg 1 times / week other, intravenous dose: 3 mg/kg route of administration: Intravenous experiment type: OTHER co-administered:	CIDOFOVIR serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.42 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7574510	5 mg/kg 1 times / week other, intravenous dose: 5 mg/kg route of administration: Intravenous experiment type: OTHER co-administered:	CIDOFOVIR serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.44 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7574510	1 mg/kg 1 times / week other, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: OTHER co-administered:	CIDOFOVIR serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
5 % single, topical Highest studied dose Dose: 5 % Route: topical Route: single Dose: 5 % Sources: https://pubmed.ncbi.nlm.nih.gov/9797239 Page: p.2998	unhealthy, 21–66 n = 96 Health Status: unhealthy Condition: Recurrent genital herpes Age Group: 21–66 Sex: M+F Population Size: 96 Sources: https://pubmed.ncbi.nlm.nih.gov/9797239 Page: p.2998	Disc. AE: Ulceration... AEs leading to discontinuation/dose reduction: Ulceration (2%) Sources: https://pubmed.ncbi.nlm.nih.gov/9797239 Page: p.2998
10 mg/kg single, intravenous Highest studied dose Dose: 10 mg/kg Route: intravenous Route: single Dose: 10 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/8739595 Page: p.154	unhealthy n = 5 Health Status: unhealthy Condition: Acquired immunodeficiency syndrome (AIDS) Sex: M+F Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/8739595 Page: p.154	Sources: https://pubmed.ncbi.nlm.nih.gov/8739595 Page: p.154
10 mg/kg single, oral Highest studied dose Dose: 10 mg/kg Route: oral Route: single Dose: 10 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/8739595 Page: p.154	unhealthy n = 5 Health Status: unhealthy Condition: Acquired immunodeficiency syndrome (AIDS) Sex: M+F Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/8739595 Page: p.154	Sources: https://pubmed.ncbi.nlm.nih.gov/8739595 Page: p.154
5 mg/kg 1 times / week multiple, intravenous Recommended Dose: 5 mg/kg, 1 times / week Route: intravenous Route: multiple Dose: 5 mg/kg, 1 times / week Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=90639fc6-0295-4115-98f0-054b783850ce&type=display Page: p.1	unhealthy Health Status: unhealthy Condition: CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS) Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=90639fc6-0295-4115-98f0-054b783850ce&type=display Page: p.1	Disc. AE: Acute renal failure... Other AEs: Renal impairment, Neutropenia... AEs leading to discontinuation/dose reduction: Acute renal failure Other AEs: Renal impairment Neutropenia Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=90639fc6-0295-4115-98f0-054b783850ce&type=display Page: p.1

AEs

AE	Significance	Dose	Population
Ulceration	2% Disc. AE	5 % single, topical Highest studied dose Dose: 5 % Route: topical Route: single Dose: 5 % Sources: https://pubmed.ncbi.nlm.nih.gov/9797239 Page: p.2998	unhealthy, 21–66 n = 96 Health Status: unhealthy Condition: Recurrent genital herpes Age Group: 21–66 Sex: M+F Population Size: 96 Sources: https://pubmed.ncbi.nlm.nih.gov/9797239 Page: p.2998
Neutropenia		5 mg/kg 1 times / week multiple, intravenous Recommended Dose: 5 mg/kg, 1 times / week Route: intravenous Route: multiple Dose: 5 mg/kg, 1 times / week Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=90639fc6-0295-4115-98f0-054b783850ce&type=display Page: p.1	unhealthy Health Status: unhealthy Condition: CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS) Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=90639fc6-0295-4115-98f0-054b783850ce&type=display Page: p.1
Renal impairment		5 mg/kg 1 times / week multiple, intravenous Recommended Dose: 5 mg/kg, 1 times / week Route: intravenous Route: multiple Dose: 5 mg/kg, 1 times / week Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=90639fc6-0295-4115-98f0-054b783850ce&type=display Page: p.1	unhealthy Health Status: unhealthy Condition: CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS) Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=90639fc6-0295-4115-98f0-054b783850ce&type=display Page: p.1
Acute renal failure	Disc. AE	5 mg/kg 1 times / week multiple, intravenous Recommended Dose: 5 mg/kg, 1 times / week Route: intravenous Route: multiple Dose: 5 mg/kg, 1 times / week Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=90639fc6-0295-4115-98f0-054b783850ce&type=display Page: p.1	unhealthy Health Status: unhealthy Condition: CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS) Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=90639fc6-0295-4115-98f0-054b783850ce&type=display Page: p.1

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	OAT1 314 OAT3 328 OCT2 336

Drug as victim

Target	Modality	Activity
OCT2 336	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/17372702/ Page: -	no
OAT1 314	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/17372702/ Page: -	yes
OAT3 328	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/17372702/ Page: -	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:3696	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:3696
ChemicalBook	CB01178278	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB01178278
ChemicalBook	CB5492709	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB5492709
Selleck Chemicals	Cidofovir	http://www.selleckchem.com/products/Cidofovir.html
ZINC	ZINC000001530600	http://zinc15.docking.org/substances/ZINC000001530600
eMolecules	2729368	https://www.emolecules.com/cgi-bin/more?vid=2729368

PubMed

Title	Date	PubMed
Comparative study of the anti-human cytomegalovirus activities and toxicities of a tetrahydrofuran phosphonate analogue of guanosine and cidofovir.	1999 Mar	10049267
Cidofovir-induced end-stage renal failure.	1999 Oct	10589927
A novel peptide aldehyde with activity against human cytomegalovirus in two different in vivo models.	2000 Jan	10693654
Economic evaluation of systemic treatments for cytomegalovirus retinitis in patients with AIDS.	2001	11465299
Vaccinia virus inhibitors as a paradigm for the chemotherapy of poxvirus infections.	2001 Apr	11292644
Human renal organic anion transporter 1 (hOAT1) and its role in the nephrotoxicity of antiviral nucleotide analogs.	2001 Apr-Jul	11563082
Cytomegalovirus treatment options in immunocompromised patients.	2001 Aug	11584992
The good and evil of HAART in HIV-related progressive multifocal leukoencephalopathy.	2001 Aug	11517417
Acute renal failure in a lung transplant patient after therapy with cidofovir.	2001 Dec	11793044
Novel non-nucleoside inhibitors of cytomegaloviruses (BAY 38-4766): in vitro and in vivo antiviral activity and mechanism of action.	2001 Dec	11733458
Long-term remission of Kaposi sarcoma-associated herpesvirus-related multicentric Castleman disease with anti-CD20 monoclonal antibody therapy.	2001 Dec 1	11719390
Treatment of lethal vaccinia virus respiratory infections in mice with cidofovir.	2001 Jan	11437324
In vitro effects of antiviral agents on human keratocytes.	2001 Jan	11189008
Failure of cidofovir therapy in progressive multifocal leukoencephalopathy unrelated to human immunodeficiency virus.	2001 Jan	11112674
Cidofovir treatment of human polyomavirus-associated acute haemorrhagic cystitis.	2001 Mar	11429040
[Anterior uveitis and cidofovir].	2001 May	11397985
Treatment of adenovirus infections in patients undergoing allogeneic hematopoietic stem cell transplantation.	2001 May 1	11303263
Successful treatment of aids related PML with HAART and cidofovir.	2001 May 29	11410399
Clinical applications of a novel sustained-release injectable drug delivery system: DepoFoam technology.	2001 May-Jun	11419030
Cidofovir as primary pre-emptive therapy for post-transplant cytomegalovirus infections.	2001 Nov	11781649
Multiple herpes simplex virus infections with various resistance patterns in a matched unrelated donor transplant recipient.	2001 Oct	11781635
Cytomegalovirus infection: the point in 2001.	2001 Oct	11737406
[Prospects for therapy and prevention of adenovirus keratoconjunctivitis].	2001 Oct	11699326
Bioterrorism. Blocking smallpox: a second defense.	2001 Oct 19	11641477
Infection due to acyclovir resistant herpes simplex virus in patients undergoing allogeneic hematopoietic stem cell transplantation.	2001 Sep	11642018
Phase II double-blind, placebo-controlled study of the safety and efficacy of cidofovir topical gel for the treatment of patients with human papillomavirus infection.	2001 Sep 1	11477525

Patents

Sample Use Guides

In Vivo Use Guide

Induction Treatment The recommended induction dose of VISTIDE (cidofovir injection) for patients with a serum creatinine of ≤1.5 mg/dL, a calculated creatinine clearance >55 mL/min, and a urine protein <100 mg/dL (equivalent to <2+ proteinuria) is 5 mg/kg body weight (given as an intravenous infusion at a constant rate over 1 hr) administered once weekly for two consecutive weeks. Maintenance Treatment The recommended maintenance dose of VISTIDE is 5 mg/kg body weight (given as an intravenous infusion at a constant rate over 1 hr), administered once every 2 weeks.

Route of Administration: Intravenous

In Vitro Use Guide

Cidofovir is active in vitro against a variety of laboratory and clinical isolates of cytomegalovirus with IC50 values of 0.5-2.8 uM (WT isolates)

Substance Class	Chemical Created by `admin` on `Fri Dec 16 23:56:39 UTC 2022` Edited by `admin` on `Fri Dec 16 23:56:39 UTC 2022`
Record UNII	M83JB37U61
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CIDOFOVIR SODIUM

Common Name

English

PHOSPHONIC ACID, ((2-(4-AMINO-2-OXO-1(2H)-PYRIMIDINYL)-1-(HYDROXYMETHYL)ETHOXY)METHYL)-, DISODIUM SALT, (S)-

Common Name

English

Code System Code Type Description

PUBCHEM

135406