BRINCIDOFOVIR SODIUM

First approved in 1996

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C27H51N3O7P.Na
Molecular Weight	583.6733
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Na+].CCCCCCCCCCCCCCCCOCCCOP([O-])(=O)CO[C@H](CO)CN1C=CC(N)=NC1=O

InChI

InChIKey=CRDDLOITBKEPRN-UQIIZPHYSA-M

InChI=1S/C27H52N3O7P.Na/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-19-35-20-16-21-37-38(33,34)24-36-25(23-31)22-30-18-17-26(28)29-27(30)32;/h17-18,25,31H,2-16,19-24H2,1H3,(H,33,34)(H2,28,29,32);/q;+1/p-1/t25-;/m0./s1

HIDE SMILES / InChI

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 18 Target ID: CHEMBL3414 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8630098	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cytomegalovirus retinitis 16 Sources: http://www.gilead.com/~/media/files/pdfs/medicines/other/vistide/vistide.pdf	Primary		Approved 8429	VISTIDE Approved Use Cidofovir injection is indicated for the treatment of cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome (AIDS). Launch Date 1996

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 326 OAT3 339 OCT2 355

Drug as victim

Target	Modality	Activity
OCT2 355	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/17372702/ Page: -	no
OAT1 326	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/17372702/ Page: -	yes
OAT3 339	substrate 3367 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
Anti-(herpes simplex virus) activity of 4'-thio-2'-deoxyuridines: a biochemical investigation for viral and cellular target enzymes.	2000 Oct 15	11023816
Adenoviral infections and a prospective trial of cidofovir in pediatric hematopoietic stem cell transplantation.	2001	11529489
Economic evaluation of systemic treatments for cytomegalovirus retinitis in patients with AIDS.	2001	11465299
Prophylaxis against herpesvirus infections in transplant recipients.	2001	11270937
Cidofovir added to highly active antiretroviral therapy in AIDS-associated progressive multifocal leukoencephalopathy.	2001 Apr 13	11371702
Infections after stem cell transplantation in children: state of the art and recommendations.	2001 Aug	11571529
Potent anti-retroviral therapy with or without cidofovir for AIDS-associated progressive multifocal leukoencephalopathy: extended follow-up of an observational study.	2001 Aug	11517418
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
Antiviral activity of NMSO3 against adenovirus in vitro.	2001 Dec	11675145
Long-term remission of Kaposi sarcoma-associated herpesvirus-related multicentric Castleman disease with anti-CD20 monoclonal antibody therapy.	2001 Dec 1	11719390
Long-term remission of an AIDS-related primary effusion lymphoma with antiviral therapy.	2001 Jan 26	11216942
The effects of cidofovir on progressive multifocal leukoencephalopathy: an MRI case study.	2001 May	11396742
Treatment of adenovirus infections in patients undergoing allogeneic hematopoietic stem cell transplantation.	2001 May 1	11303263
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
Successful treatment of foscarnet-resistant herpes simplex stomatitis with intravenous cidofovir in a child.	2001 Nov	11734717
Cidofovir treatment of progressive multifocal leukoencephalopathy in a patient receiving highly active antiretroviral therapy.	2001 Nov	11702907
Prevention and inhibition of nasopharyngeal carcinoma growth by antiviral phosphonated nucleoside analogs.	2001 Nov 1	11691806
Multiple herpes simplex virus infections with various resistance patterns in a matched unrelated donor transplant recipient.	2001 Oct	11781635
Cidofovir for KS lesions.	2001 Oct	11768871
[Prospects for therapy and prevention of adenovirus keratoconjunctivitis].	2001 Oct	11699326
Effects of cidofovir on the pathogenesis of a lethal vaccinia virus respiratory infection in mice.	2001 Oct	11530188
Bioterrorism. Blocking smallpox: a second defense.	2001 Oct 19	11641477
Cidofovir-induced end-stage renal failure.	2002 Jan	11773481

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)

Name

Type

Language

BRINCIDOFOVIR SODIUM

Common Name

English

PHOSPHONIC ACID, (((1S)-2-(4-AMINO-2-OXO-1(2H)-PYRIMIDINYL)-1-(HYDROXYMETHYL)ETHOXY)METHYL)-, MONO(3-(HEXADECYLOXY)PROPYL) ESTER, MONOSODIUM SALT

Common Name

English

PHOSPHONIC ACID, P-(((1S)-2-(4-AMINO-2-OXO-1(2H)-PYRIMIDINYL)-1-(HYDROXYMETHYL)ETHOXY)METHYL)-, MONO(3-(HEXADECYLOXY)PROPYL)ESTER, SODIUM SALT (1:1)

Common Name

English

HEXADECYLOXYPROPYL-CIDOFOVIR SODIUM

Common Name

English

SODIUM 3-(HEXADECYLOXY)PROPYL (((1S)-2-(4-AMINO-2-OXOPYRIMIDIN-1(2H)-YL)-1-(HYDROXYMETHYL)ETHOXY)METHYL)PHOSPHONATE

Systematic Name

English

Code System Code Type Description

PUBCHEM

24848765