didanosine 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
antivirals 869 69655-05-6

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • didanosine
  • videx
  • dideoxyinosine
A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. Didanosine is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase; ddI is then metabolized to dideoxyadenosine triphosphate, its putative active metabolite.
  • Molecular weight: 236.23
  • Formula: C10H12N4O3
  • CLOGP: -1.12
  • LIPINSKI: 0
  • HAC: 7
  • HDO: 2
  • TPSA: 88.74
  • ALOGS: -1.56
  • ROTB: 2
  • Status: OFM
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.40 g O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 3 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 27.30 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 55 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 24.19 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 38 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 0.77 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 11 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.95 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 1.40 hours Lombardo F, Berellini G, Obach RS

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 -0.991 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 9.141 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 1.690 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 1.377 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 89 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 92.210 % High 1
herg hERG pIC50 3.626 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 1.197 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 3.192 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 85.170 % High 1
kinase-safety-class ACVR2B,AXL,CAMK2D,CDK5,CDK9,DYRK1B,EIF2AK3,ERBB2,FLT3,GRK2,ITK,MAP3K21,PDK1,PDK2,PRKDC 15
kinase-selectivity-class PDK1 1
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 2.938 High 1
mh-clint Mouse hepatocyte intrinsic clearance 2.254 High 1
mppb Mouse plasma protein binding (% unbound) 92.630 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 2.559 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 93.680 % High 1
rh-clint Rat hepatocyte intrinsic clearance 1.517 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 95.450 % High 1
rppb Rat plasma protein binding (% unbound) 85.650 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 883.080 uM High 1

Approvals:

DateAgencyCompanyOrphan
Oct. 9, 1991 FDA BRISTOL MYERS SQUIBB

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Viral mutation identified 393.06 104.02 61 1568 1964 90624854
Pregnancy 358.35 104.02 101 1528 61946 90564872
Foetal exposure during pregnancy 336.67 104.02 89 1540 42886 90583932
Drug resistance 257.02 104.02 67 1562 30382 90596436
Retinal toxicity 196.58 104.02 32 1597 1390 90625428
Caesarean section 186.52 104.02 47 1582 18530 90608288
Pathogen resistance 140.97 104.02 32 1597 8083 90618735
Abortion induced 133.86 104.02 33 1596 11855 90614963
Stillbirth 132.79 104.02 30 1599 7413 90619405
Virologic failure 110.72 104.02 21 1608 2203 90624615
Premature rupture of membranes 107.84 104.02 24 1605 5534 90621284
Premature delivery 107.10 104.02 36 1593 38726 90588092

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Lipodystrophy acquired 838.19 52.77 153 2832 3297 42615053
Mitochondrial toxicity 739.74 52.77 132 2853 2483 42615867
Eyelid ptosis 673.88 52.77 142 2843 6519 42611831
Diplopia 443.00 52.77 126 2859 20190 42598160
Progressive external ophthalmoplegia 377.19 52.77 68 2917 1343 42617007
Foetal exposure during pregnancy 330.95 52.77 124 2861 47187 42571163
Pinealoblastoma 265.23 52.77 38 2947 149 42618201
Viral mutation identified 251.68 52.77 56 2929 3275 42615075
Virologic failure 246.89 52.77 57 2928 3937 42614413
Retinal toxicity 218.95 52.77 37 2948 490 42617860
Pathogen resistance 195.97 52.77 59 2926 11391 42606959
Hepatic fibrosis 175.36 52.77 45 2940 4827 42613523
Ophthalmoplegia 166.19 52.77 37 2948 2163 42616187
Drug resistance 126.49 52.77 57 2928 34191 42584159
Drug-induced liver injury 123.52 52.77 58 2927 38215 42580135
Portal hypertension 91.95 52.77 27 2958 4760 42613590
Dysphagia 86.21 52.77 57 2928 72662 42545688
Mitochondrial myopathy 82.40 52.77 14 2971 191 42618159
Congenital neoplasm 71.82 52.77 10 2975 30 42618320
Blood lactic acid increased 70.50 52.77 25 2960 8014 42610336
Strongyloidiasis 59.99 52.77 18 2967 3413 42614937
Dyslipidaemia 59.43 52.77 23 2962 9395 42608955
Optic nerve neoplasm 56.51 52.77 8 2977 28 42618322
Premature baby 56.38 52.77 29 2956 23124 42595226
Multiple-drug resistance 53.85 52.77 20 2965 7302 42611048
Retinopathy 53.33 52.77 15 2970 2266 42616084

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Lipodystrophy acquired 973.74 64.04 162 3495 4362 110581280
Mitochondrial toxicity 838.35 64.04 136 3521 3109 110582533
Eyelid ptosis 663.89 64.04 139 3518 13188 110572454
Viral mutation identified 627.08 64.04 111 3546 4308 110581334
Diplopia 441.29 64.04 125 3532 41769 110543873
Progressive external ophthalmoplegia 427.59 64.04 68 3589 1352 110584290
Retinal toxicity 417.02 64.04 68 3589 1591 110584051
Drug resistance 350.26 64.04 112 3545 56262 110529380
Virologic failure 324.69 64.04 65 3592 4887 110580755
Pathogen resistance 305.14 64.04 78 3579 17594 110568048
Foetal exposure during pregnancy 253.58 64.04 57 3600 7448 110578194
Pregnancy 231.18 64.04 80 3577 50987 110534655
Hepatic fibrosis 201.83 64.04 48 3609 8018 110577624
Ophthalmoplegia 170.42 64.04 36 3621 3514 110582128
Caesarean section 135.09 64.04 39 3618 13778 110571864
Retinopathy 129.94 64.04 30 3627 4399 110581243
Portal hypertension 119.43 64.04 32 3625 8605 110577037
Drug-induced liver injury 115.60 64.04 63 3594 120004 110465638
Abortion induced 107.52 64.04 29 3628 7990 110577652
Multiple-drug resistance 101.64 64.04 31 3626 13204 110572438
Drug interaction 92.02 64.04 97 3560 500086 110085556
Dysphagia 91.17 64.04 59 3598 153541 110432101
Dyslipidaemia 87.82 64.04 29 3628 15936 110569706
Mitochondrial myopathy 81.77 64.04 14 3643 440 110585202
Pinealoblastoma 81.69 64.04 11 3646 62 110585580
Retinoblastoma 79.14 64.04 11 3646 81 110585561
Premature delivery 76.19 64.04 31 3626 30601 110555041
Stillbirth 69.47 64.04 18 3639 4246 110581396
Strongyloidiasis 66.68 64.04 18 3639 4968 110580674

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC J05AF02 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS
Nucleoside and nucleotide reverse transcriptase inhibitors
FDA MoA N0000009947 Nucleoside Reverse Transcriptase Inhibitors
FDA EXT N0000175459 Nucleoside Analog
FDA EPC N0000175462 Human Immunodeficiency Virus Nucleoside Analog Reverse Transcriptase Inhibitor
MeSH PA D000890 Anti-Infective Agents
MeSH PA D000963 Antimetabolites
MeSH PA D000998 Antiviral Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D018894 Reverse Transcriptase Inhibitors
MeSH PA D019380 Anti-HIV Agents
MeSH PA D019384 Nucleic Acid Synthesis Inhibitors
CHEBI has role CHEBI:22587 antiviral agent
CHEBI has role CHEBI:33231 antitubercular agent
CHEBI has role CHEBI:35221 antimetabolite
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:36044 antiviral drug
CHEBI has role CHEBI:53756 HIV-1 reverse transcriptase inhibitor
CHEBI has role CHEBI:63090 EC 2.4.2.1 (purine-nucleoside phosphorylase) inhibitor
CHEBI has role CHEBI:64946 anti-HIV agent
CHEBI has role CHEBI:176497 geroprotector

Related Drugs by ATC class:

J05AF Nucleoside and nucleotide reverse transcriptase inhibitors 12 drugs
abacaviradefovir dipivoxilclevudineemtricitabineentecavirlamivudinestavudinetelbivudinetenofovir alafenamidetenofovir disoproxilzalcitabinezidovudine

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Human immunodeficiency virus infection indication 86406008 DOID:526
Prevention of HIV Infection after Exposure off-label use
Metabolic alkalosis contraindication 1388004
Anuria contraindication 2472002 DOID:2983
Hypophosphatemia contraindication 4996001
Hypocalcemia contraindication 5291005
Alcoholism contraindication 7200002
Hypercholesterolemia contraindication 13644009
Hyperkalemia contraindication 14140009
Constipation contraindication 14760008 DOID:2089
Pulmonary edema contraindication 19242006 DOID:11396
Retinal disorder contraindication 29555009 DOID:5679
Sarcoidosis contraindication 31541009 DOID:11335
Dehydration contraindication 34095006
Portal hypertension contraindication 34742003 DOID:10762
Hyperuricemia contraindication 35885006 DOID:1920
Hypertensive disorder contraindication 38341003 DOID:10763
Hypernatremia contraindication 39355002
Fecal impaction contraindication 44635007
Chronic heart failure contraindication 48447003
Acute nephropathy contraindication 58574008
Diarrhea contraindication 62315008
Optic neuritis contraindication 66760008 DOID:1210
Hypercalcemia contraindication 66931009 DOID:12678
Hyperparathyroidism contraindication 66999008 DOID:13543
Hemorrhoids contraindication 70153002 DOID:9746
Diabetes mellitus contraindication 73211009 DOID:9351
Pancreatitis contraindication 75694006 DOID:4989
Oliguria contraindication 83128009
Kidney disease contraindication 90708001 DOID:557
Lactic acidosis contraindication 91273001 DOID:3650
Kidney stone contraindication 95570007
Gastrointestinal obstruction contraindication 126765001
Steatosis of liver contraindication 197321007
Impaired renal function disorder contraindication 197663003
Osteolysis contraindication 203522001
Myocardial dysfunction contraindication 233928007
Disease of liver contraindication 235856003 DOID:409
Chronic diarrhea contraindication 236071009
Aluminum intoxication contraindication 236546003
Peripheral edema contraindication 271809000
Peripheral nerve disease contraindication 302226006
Hypertriglyceridemia contraindication 302870006
Familial hyperkalemic periodic paralysis contraindication 304737009 DOID:14451
Adrenal cortical hypofunction contraindication 386584007 DOID:10493
Cardiovascular event risk contraindication 395112001
Breastfeeding (mother) contraindication 413712001
Disorder of coronary artery contraindication 414024009
Obesity contraindication 414916001 DOID:9970
Azotemia contraindication 445009001
Smokes tobacco daily contraindication 449868002
Severe dehydration contraindication 450316000




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 8.94 acidic
pKa2 12.68 acidic
pKa3 1.93 Basic
pKa4 0.76 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Reverse transcriptase/RNaseH Enzyme INHIBITOR IC50 5.21 WOMBAT-PK CHEMBL

External reference:

IDSource
4020118 VUID
N0000148104 NUI
D00296 KEGG_DRUG
152494 RXNORM
4020118 VANDF
C0012133 UMLSCUI
CHEBI:490877 CHEBI
2DI PDB_CHEM_ID
CHEMBL1460 ChEMBL_ID
DB00900 DRUGBANK_ID
D016049 MESH_DESCRIPTOR_UI
135398739 PUBCHEM_CID
4833 IUPHAR_LIGAND_ID
6664 INN_ID
K3GDH6OH08 UNII
4588 MMSL
63947 MMSL
854 MMSL
d00078 MMSL
003604 NDDF
19194001 SNOMEDCT_US
387105006 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Didanosine HUMAN PRESCRIPTION DRUG LABEL 1 53808-0236 CAPSULE, DELAYED RELEASE PELLETS 250 mg ORAL ANDA 27 sections
Didanosine HUMAN PRESCRIPTION DRUG LABEL 1 53808-0353 CAPSULE, DELAYED RELEASE PELLETS 400 mg ORAL ANDA 27 sections
Didanosine HUMAN PRESCRIPTION DRUG LABEL 1 54868-5464 CAPSULE, DELAYED RELEASE PELLETS 250 mg ORAL ANDA 28 sections