DIDANOSINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C10H12N4O3
Molecular Weight	236.2273
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

OC[C@@H]1CC[C@@H](O1)N2C=NC3=C2N=CNC3=O

InChI

InChIKey=BXZVVICBKDXVGW-NKWVEPMBSA-N

InChI=1S/C10H12N4O3/c15-3-6-1-2-7(17-6)14-5-13-8-9(14)11-4-12-10(8)16/h4-7,15H,1-3H2,(H,11,12,16)/t6-,7+/m0/s1

HIDE SMILES / InChI

Molecular Formula	C10H12N4O3
Molecular Weight	236.2273
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description

Didanosine was developed by Bristol-Myers Squibb in collaboration with the NIH for the treatment of HIV-1 infections. Upon administration the drug is metabolized to the active metabolite which inhibits HIV-1 reverse transcriptase both by competing with deoxyadenosine 5'-triphosphate and by its incorporation into viral DNA. Didanosine was approved by FDA under the name Videx (among the other names).

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Human immunodeficiency virus type 1 reverse transcriptase 67	Inhibitor 8,297

Conditions

Condition	Modality	Targets	Highest Phase	Product
HIV-1 infection 151	Primary		Approved 8,429	VIDEX

C_max

Value	Dose	Analyte	Population
305 ng/mL	0.4 mg/kg bw single, intravenous	DIDANOSINE plasma	Homo sapiens
291 ng/mL	0.4 mg/kg bw 2 times / day steady-state, intravenous	DIDANOSINE plasma	Homo sapiens
2818 ng/mL	3 mg/kg bw single, intravenous	DIDANOSINE plasma	Homo sapiens
3041 ng/mL	3 mg/kg bw 2 times / day steady-state, intravenous	DIDANOSINE plasma	Homo sapiens
17974 ng/mL	16.5 mg/kg bw single, intravenous	DIDANOSINE plasma	Homo sapiens
18019 ng/mL	16.5 mg/kg bw 2 times / day steady-state, intravenous	DIDANOSINE plasma	Homo sapiens
244 ng/mL	0.8 mg/kg bw single, oral	DIDANOSINE plasma	Homo sapiens
343 ng/mL	0.8 mg/kg bw 2 times / day steady-state, oral	DIDANOSINE plasma	Homo sapiens
1494 ng/mL	6 mg/kg bw single, oral	DIDANOSINE plasma	Homo sapiens
2257 ng/mL	6 mg/kg bw 2 times / day steady-state, oral	DIDANOSINE plasma	Homo sapiens
5787 ng/mL	33 mg/kg bw single, oral	DIDANOSINE plasma	Homo sapiens
6041 ng/mL	33 mg/kg bw 2 times / day steady-state, oral	DIDANOSINE plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
413 ng × h/mL	0.4 mg/kg bw single, intravenous	DIDANOSINE plasma	Homo sapiens
418 ng × h/mL	0.4 mg/kg bw 2 times / day steady-state, intravenous	DIDANOSINE plasma	Homo sapiens
3726 ng × h/mL	3 mg/kg bw single, intravenous	DIDANOSINE plasma	Homo sapiens
4118 ng × h/mL	3 mg/kg bw 2 times / day steady-state, intravenous	DIDANOSINE plasma	Homo sapiens
28257 ng × h/mL	16.5 mg/kg bw single, intravenous	DIDANOSINE plasma	Homo sapiens
32264 ng × h/mL	16.5 mg/kg bw 2 times / day steady-state, intravenous	DIDANOSINE plasma	Homo sapiens
351 ng × h/mL	0.8 mg/kg bw single, oral	DIDANOSINE plasma	Homo sapiens
421 ng × h/mL	0.8 mg/kg bw 2 times / day steady-state, oral	DIDANOSINE plasma	Homo sapiens
2374 ng × h/mL	6 mg/kg bw single, oral	DIDANOSINE plasma	Homo sapiens
3377 ng × h/mL	6 mg/kg bw 2 times / day steady-state, oral	DIDANOSINE plasma	Homo sapiens
12730 ng × h/mL	33 mg/kg bw single, oral	DIDANOSINE plasma	Homo sapiens
14179 ng × h/mL	33 mg/kg bw 2 times / day steady-state, oral	DIDANOSINE plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
0.88 h	0.4 mg/kg bw single, intravenous	DIDANOSINE plasma	Homo sapiens
0.93 h	0.4 mg/kg bw 2 times / day steady-state, intravenous	DIDANOSINE plasma	Homo sapiens
1.17 h	3 mg/kg bw single, intravenous	DIDANOSINE plasma	Homo sapiens
1.19 h	3 mg/kg bw 2 times / day steady-state, intravenous	DIDANOSINE plasma	Homo sapiens
1.48 h	16.5 mg/kg bw single, intravenous	DIDANOSINE plasma	Homo sapiens
1.49 h	16.5 mg/kg bw 2 times / day steady-state, intravenous	DIDANOSINE plasma	Homo sapiens
0.76 h	0.8 mg/kg bw single, oral	DIDANOSINE plasma	Homo sapiens
1.1 h	0.8 mg/kg bw 2 times / day steady-state, oral	DIDANOSINE plasma	Homo sapiens
1.12 h	6 mg/kg bw single, oral	DIDANOSINE plasma	Homo sapiens
1.24 h	6 mg/kg bw 2 times / day steady-state, oral	DIDANOSINE plasma	Homo sapiens
1.64 h	33 mg/kg bw single, oral	DIDANOSINE plasma	Homo sapiens
1.9 h	33 mg/kg bw 2 times / day steady-state, oral	DIDANOSINE plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
25 mg/kg 1 times / day steady, oral Highest studied dose	unhealthy, 0.7 - 18.9 years	DLT: Neuropathy, Pancreatitis...
12.8 mg/kg 1 times / day steady, oral Recommended	unhealthy, 0.7 - 18.9 years	DLT: Neuropathy, Pancreatitis...
13 mg/kg 1 times / day steady, oral Recommended	unhealthy, 0.7 - 18.9 years	DLT: Pancreatitis...
20.5 mg/kg 1 times / day steady, oral Recommended	unhealthy, 0.7 - 18.9 years	DLT: Neuropathy, Pancreatitis...
500 mg 1 times / day steady, oral Recommended	unhealthy, adult	DLT: Neutropenia, Neutropenia... Disc. AE: Anemia, Thrombocytopenia...

Showing 1 to 5 of 5 entries

Previous1Next

AEs

Show entries

AE	Significance	Dose	Population
Neuropathy	13 patients DLT, Disc. AE	25 mg/kg 1 times / day steady, oral Highest studied dose	unhealthy, 0.7 - 18.9 years
Pancreatitis	6 patients DLT, Disc. AE	25 mg/kg 1 times / day steady, oral Highest studied dose	unhealthy, 0.7 - 18.9 years
Pancreatitis	1 patient DLT, Disc. AE	12.8 mg/kg 1 times / day steady, oral Recommended	unhealthy, 0.7 - 18.9 years
Neuropathy	5 patients DLT, Disc. AE	12.8 mg/kg 1 times / day steady, oral Recommended	unhealthy, 0.7 - 18.9 years
Pancreatitis	grade 5, 0.35% DLT, Disc. AE	13 mg/kg 1 times / day steady, oral Recommended	unhealthy, 0.7 - 18.9 years

Showing 1 to 5 of 16 entries

Previous1 2 3 4Next

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BCRP 699	BCRP 561

Drug as perpetrator

Show entries

Target	Modality	Activity	Metabolite	Clinical evidence
BCRP 773	inhibitor 3,277	no

Showing 1 to 1 of 1 entries

Previous1Next

Drug as victim

Show entries

Target	Modality	Activity	Metabolite	Clinical evidence
BCRP 561	substrate 3,367	likely

Showing 1 to 1 of 1 entries

Previous1Next

Sourcing

Sourcing

Show entries

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:490877	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:490877
ChemicalBook	CB0680765	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB0680765
eMolecules	1986517	https://www.emolecules.com/cgi-bin/more?vid=1986517
eMolecules	2724662	https://www.emolecules.com/cgi-bin/more?vid=2724662
eMolecules	30075948	https://www.emolecules.com/cgi-bin/more?vid=30075948

Showing 1 to 5 of 11 entries

Previous1 2 3Next

PubMed

Show entries

Title	Date	PubMed
Effect of nucleoside analogs and non-nucleoside inhibitors of HIV-1 reverse transcriptase on cell-free virions.	1999	10226617
Hydroxyurea-induced neurotoxicity in HIV disease.	1999 Aug 20	10465092
In vitro induction of human immunodeficiency virus type 1 variants resistant to phosphoralaninate prodrugs of Z-methylenecyclopropane nucleoside analogues.	1999 Oct	10508028
In vitro selection of mutations in the human immunodeficiency virus type 1 reverse transcriptase that decrease susceptibility to (-)-beta-D-dioxolane-guanosine and suppress resistance to 3'-azido-3'-deoxythymidine.	2000 Jul	10858331
Resolution of chronic parvovirus b19-induced anemia, by use of highly active antiretroviral therapy, in a patient with acquired immunodeficiency syndrome.	2001 Apr 1	11264051

Showing 1 to 5 of 15 entries

Previous1 2 3Next

Patents

Sample Use Guides

In Vivo Use Guide

In adult patients didanosine should be administered on an empty stomach at least 30 minutes before eating at the dose of 200 mg twice daily (body weight is at least 60 kg) or 125 mg twice daily (body weight is less than 60 kg). Pediatric patients (2 weeks old to 18 years old): the drug should be administered on an empty stomach at least 30 minutes before or 2 hours after eating at the dose of 100-120 mg per m2 twice daily.

Route of Administration: Oral

In Vitro Use Guide

The anti-HIV-1 activity of didanosine was evaluated in a variety of HIV-1 infected lymphoblastic cell lines and monocyte/macrophage cell cultures. The concentration of drug necessary to inhibit viral replication by 50% (EC50) ranged from 2.5 to 10 uM (1 uM = 0.24 ug/mL) in lymphoblastic cell lines and 0.01 to 0.1 uM in monocyte/macrophage cell cultures.

Substance Class	Chemical
Record UNII	K3GDH6OH08
Record Status	`Validated (UNII)`
Record Version

Show entries

Name

Type

Language

DIDANOSINE

Official Name

English

DIDANOSINE [MI]

Common Name

English

(-)-DIDANOSINE

Common Name

English

didanosine [INN]

Common Name

English

DIDANOSINUM [WHO-IP LATIN]

Common Name

English

Showing 1 to 5 of 25 entries

Previous1 2 3 4 5Next

Show entries

Classification Tree

Code System

Code

Reverse Transcriptase Inhibitors

NDF-RT

N0000009947

Nucleoside and nucleotide reverse transcriptase inhibitors

WHO-VATC

QJ05AF02

Nucleosides

NDF-RT

N0000175459

Reverse Transcriptase Inhibitor

NCI_THESAURUS

C97452

Nucleoside and nucleotide reverse transcriptase inhibitors

WHO-ATC

J05AF02

Showing 1 to 5 of 11 entries

Previous1 2 3Next

Show entries

Code System

Code

Type

Description

MERCK INDEX

m4379

PRIMARY

Merck Index

EVMPD

SUB07104MIG

PRIMARY

HSDB

6548

PRIMARY

PUBCHEM

135398739

PRIMARY

EPA CompTox

DTXSID6022927

PRIMARY

Showing 1 to 5 of 24 entries

Previous1 2 3 4 5Next

Show entries

Related Record

Type

Details


					K3GDH6OH08

DIDANOSINE

BASIS OF STRENGTH->SUBSTANCE

Interaction Type:

ASSAY (HPLC)

Qualification:

USP

Amount:

RELATIONSHIP_AMOUNT [98 to 102] WEIGHT PERCENT (limits)


					K3GDH6OH08

DIDANOSINE

BASIS OF STRENGTH->SUBSTANCE

Interaction Type:

ASSAY (TITRATION)

Qualification:

EP

Amount:

RELATIONSHIP_AMOUNT [98.5 to 101] WEIGHT PERCENT (limits)


					A3Z87NSO0U

HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 POLYMERASE

TARGET -> INHIBITOR

Amount:


					859A956UY8

HUMAN IMMUNODEFICIENCY VIRUS TYPE 1

TARGET ORGANISM->INHIBITOR

Amount:

Showing 1 to 4 of 4 entries

Previous1Next

Show entries

Related Record

Type

Details


					HN0RQ6SBWQ

2'-DEOXYINOSINE

IMPURITY -> PARENT

Interaction Type:

CHROMATOGRAPHIC PURITY (HPLC/UV)

Qualification:

USP

Amount:

RELATIONSHIP_AMOUNT [<0.3] PERCENT PEAK AREA (limits)


					J71U8QAU3Q

3'-DEOXYINOSINE

IMPURITY -> PARENT

Interaction Type:

CHROMATOGRAPHIC PURITY (HPLC/UV)

Qualification:

USP

Amount:

RELATIONSHIP_AMOUNT [<0.2] PERCENT PEAK AREA (limits)


					5A614L51CT

INOSINE

IMPURITY -> PARENT

Interaction Type:

CHROMATOGRAPHIC PURITY (HPLC/UV)

Qualification:

EP

Amount:

RELATIONSHIP_AMOUNT [<0.2] (limits)


					HN0RQ6SBWQ

2'-DEOXYINOSINE

IMPURITY -> PARENT

Interaction Type:

CHROMATOGRAPHIC PURITY (HPLC/UV)

Qualification:

EP

Amount:

RELATIONSHIP_AMOUNT [<0.2] PERCENT PEAK AREA (limits)


					2TN51YD919

HYPOXANTHINE

IMPURITY -> PARENT

Interaction Type:

CHROMATOGRAPHIC PURITY (HPLC/UV)

Qualification:

EP

Amount:

RELATIONSHIP_AMOUNT [<0.5] PERCENT PEAK AREA (limits)

Showing 1 to 5 of 21 entries

Previous1 2 3 4 5Next

Show entries

Related Record

Type

Details


					K3GDH6OH08

DIDANOSINE

ACTIVE MOIETY

Amount:

Showing 1 to 1 of 1 entries

Previous1Next

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

Drug as perpetrator