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

Stem definitionDrug idCAS RN
antivirals 88 142340-99-6

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • adefovir dipivoxil
  • hepsera
  • preveon
inhibitor of African swine fever virus
  • Molecular weight: 501.48
  • Formula: C20H32N5O8P
  • CLOGP: 1.40
  • LIPINSKI: 2
  • HAC: 13
  • HDO: 1
  • TPSA: 166.98
  • ALOGS: -2.90
  • ROTB: 15
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
10 mg O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Bocci G, Oprea TI, Benet LZ
S (Water solubility) 0.40 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 45 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.43 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 12 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 1.699 Moderate 0.66
caco2-efflux Caco-2 efflux ratio (BA/AB) 3.381 Moderate 0.66
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 24.044 10^-6 cm/s Moderate 0.66
dh-clint Dog hepatocyte intrinsic clearance 422.669 uL/min/10^6 cells Moderate 0.66
dppb Dog plasma protein binding (% unbound) 23.320 % Moderate 0.66
fcs-ppb Fetal calf serum protein binding (% unbound) 8.170 % Moderate 0.66
herg hERG pIC50 4.055 pIC50 Moderate 0.66
hh-clint Human hepatocyte intrinsic clearance 966.051 uL/min/10^6 cells Moderate 0.66
hlm-clint Human liver microsomal intrinsic clearance 304.089 uL/min/mg protein Moderate 0.66
hppb Human plasma protein binding (% unbound) 11.160 % Moderate 0.66
kinase-safety-class ACVR2B,AURKA,AXL,BRAF,CAMK2D,CDK5,CDK9,DDR1,DYRK1B,EIF2AK3,ERBB2,FLT3,GRK2,ITK,MAP3K1,MAP3K21,MAPK7,MARK4,NTRK2,PDK1,PDK2,PIK3CD,PRKDC,SIK2,STK33,TEK,TTK 27
kinase-selectivity-class AXL,BRAF,GRK2,MAP3K21 4
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 10.447 Moderate 0.66
mh-clint Mouse hepatocyte intrinsic clearance 1489.361 Moderate 0.66
mppb Mouse plasma protein binding (% unbound) 27.500 Moderate 0.66
pfas-class PFAS structural alert (1 = True, 0 = False) 0
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 13.521 Moderate 0.66
pld-class Phospholipidosis risk class (1 = positive, 0 = negative) 0 Moderate 0.66
pppb Pig plasma protein binding (% unbound) 20.450 % Moderate 0.66
rh-clint Rat hepatocyte intrinsic clearance 389.045 uL/min/10^6 cells Moderate 0.66
rh-fuinc Rat hepatocyte fraction unbound in incubation 90.120 % Moderate 0.66
rppb Rat plasma protein binding (% unbound) 24.580 % Moderate 0.66
solubility-dd Solubility at pH 7.4 in DMSO 362.243 uM Moderate 0.66

Approvals:

DateAgencyCompanyOrphan
March 6, 2003 EMA
Sept. 20, 2002 FDA GILEAD

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
Osteomalacia 543.32 71.37 71 1221 824 90626331
Fanconi syndrome acquired 387.07 71.37 55 1237 1219 90625936
Hypophosphataemia 269.06 71.37 58 1234 14796 90612359
Drug resistance 212.91 71.37 55 1237 30394 90596761
Hypophosphataemic osteomalacia 178.88 71.37 23 1269 228 90626927
Osteoporosis 157.85 71.37 57 1235 96474 90530681
Bone pain 145.51 71.37 48 1244 61935 90565220
Fanconi syndrome 118.45 71.37 21 1271 1922 90625233
Pathogen resistance 73.09 71.37 18 1274 8097 90619058
Viral mutation identified 72.68 71.37 14 1278 2011 90625144

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
Osteomalacia 1624.83 67.19 236 4167 648 42616284
Fanconi syndrome acquired 731.28 67.19 134 4269 1936 42614996
Hypophosphataemia 689.18 67.19 195 4208 20750 42596182
Drug resistance 463.92 67.19 162 4241 34086 42582846
Hypophosphataemic osteomalacia 428.26 67.19 60 4343 111 42616821
Osteoporosis 397.10 67.19 118 4285 14788 42602144
Viral mutation identified 367.93 67.19 82 4321 3249 42613683
Fanconi syndrome 358.06 67.19 72 4331 1722 42615210
Blood phosphorus decreased 324.15 67.19 75 4328 3518 42613414
Bone pain 311.92 67.19 110 4293 23682 42593250
Pathogen resistance 189.06 67.19 63 4340 11387 42605545
Hypouricaemia 177.61 67.19 30 4373 258 42616674
Blood alkaline phosphatase increased 172.00 67.19 79 4324 33518 42583414
Hepatitis B DNA increased 168.66 67.19 32 4371 557 42616375
Multiple fractures 148.51 67.19 34 4369 1514 42615418
Bone density decreased 141.56 67.19 35 4368 2171 42614761
Multiple-drug resistance 131.70 67.19 43 4360 7279 42609653
Renal tubular disorder 126.70 67.19 38 4365 4871 42612061
Viral load increased 121.51 67.19 33 4370 2964 42613968
Urine phosphorus increased 111.39 67.19 18 4385 114 42616818
Glycosuria 104.57 67.19 25 4378 1345 42615587
Hepatitis B reactivation 103.45 67.19 32 4371 4546 42612386
Renal tubular dysfunction 95.17 67.19 19 4384 435 42616497
Hepatocellular carcinoma 92.54 67.19 34 4369 8160 42608772
Genotype drug resistance test positive 92.04 67.19 22 4381 1182 42615750
Blood creatinine increased 88.03 67.19 80 4323 109923 42507009
Hepatitis B 83.82 67.19 30 4373 6681 42610251
Gait disturbance 83.79 67.19 74 4329 97926 42519006
Urine calcium increased 82.56 67.19 12 4391 32 42616900
Arthralgia 75.46 67.19 99 4304 205139 42411793
Bone marrow oedema 72.11 67.19 17 4386 860 42616072

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
Osteomalacia 2133.44 62.46 293 5025 1294 110582687
Fanconi syndrome acquired 1068.74 62.46 175 5143 2859 110581122
Hypophosphataemia 960.12 62.46 238 5080 32944 110551037
Hypophosphataemic osteomalacia 605.03 62.46 83 5235 354 110583627
Drug resistance 551.46 62.46 173 5145 56201 110527780
Viral mutation identified 498.08 62.46 97 5221 4322 110579659
Osteoporosis 429.26 62.46 160 5158 86992 110496989
Fanconi syndrome 425.83 62.46 82 5236 3437 110580544
Bone pain 419.99 62.46 146 5172 64987 110518994
Blood phosphorus decreased 335.25 62.46 77 5241 7588 110576393
Pathogen resistance 285.02 62.46 80 5238 17592 110566389
Blood alkaline phosphatase increased 221.92 62.46 94 5224 70841 110513140
Hypouricaemia 214.98 62.46 35 5283 543 110583438
Viral load increased 191.49 62.46 42 5276 3348 110580633
Renal tubular disorder 173.17 62.46 45 5273 7384 110576597
Hepatitis B DNA increased 167.90 62.46 30 5288 825 110583156
Hepatitis B reactivation 163.21 62.46 43 5275 7441 110576540
Renal tubular dysfunction 160.16 62.46 29 5289 861 110583120
Multiple-drug resistance 156.03 62.46 47 5271 13188 110570793
Glycosuria 150.85 62.46 33 5285 2597 110581384
Urine phosphorus increased 143.56 62.46 21 5297 152 110583829
Bone density decreased 126.81 62.46 42 5276 16000 110567981
Hepatocellular carcinoma 124.74 62.46 37 5281 9843 110574138
Genotype drug resistance test positive 122.95 62.46 25 5293 1381 110582600
Multiple fractures 115.14 62.46 34 5284 8906 110575075
Proteinuria 108.52 62.46 48 5270 39970 110544011
Renal impairment 108.18 62.46 82 5236 188363 110395618
Blood creatinine increased 105.90 62.46 80 5238 182809 110401172
Gait disturbance 97.42 62.46 91 5227 278117 110305864
Glucose urine present 84.19 62.46 20 5298 2269 110581712
Nephropathy toxic 81.11 62.46 35 5283 27443 110556538
Acquired aminoaciduria 81.11 62.46 10 5308 13 110583968
Urine calcium increased 79.80 62.46 12 5306 107 110583874
Renal glycosuria 77.80 62.46 10 5308 22 110583959
Femoral neck fracture 76.26 62.46 27 5291 12540 110571441
Rib fracture 74.20 62.46 35 5283 33735 110550246
Blood uric acid decreased 70.60 62.46 16 5302 1477 110582504
Hyperphosphatasaemia 70.17 62.46 11 5307 132 110583849
Bone marrow oedema 69.83 62.46 17 5301 2139 110581842
Renal tubular acidosis 65.40 62.46 19 5299 4696 110579285
Urine phosphorus decreased 65.06 62.46 9 5309 41 110583940
Hyperphosphaturia 62.98 62.46 10 5308 131 110583850

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC J05AF08 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
CHEBI has role CHEBI:36044 antiviral drug
CHEBI has role CHEBI:49103 drug metabolite
CHEBI has role CHEBI:50909 nephrotoxic agent
CHEBI has role CHEBI:53756 HIV-1 reverse transcriptase inhibitor
CHEBI has role CHEBI:59517 DNA synthesis inhibitor
CHEBI has role CHEBI:64946 anti-HIV agent
CHEBI has role CHEBI:64951 anti-HBV agent
MeSH PA D000890 Anti-Infective Agents
MeSH PA D000998 Antiviral Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D018894 Reverse Transcriptase Inhibitors
MeSH PA D019384 Nucleic Acid Synthesis Inhibitors
FDA EPC N0000175656 Hepatitis B Virus Nucleoside Analog Reverse Transcriptase Inhibitor

Related Drugs by ATC class:

J05AF Nucleoside and nucleotide reverse transcriptase inhibitors 12 drugs
abacavirclevudinedidanosineemtricitabineentecavirlamivudinestavudinetelbivudinetenofovir alafenamidetenofovir disoproxilzalcitabinezidovudine

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

DiseaseRelationSNOMED_IDDOID
Chronic type B viral hepatitis indication 61977001
Kidney disease contraindication 90708001 DOID:557
Lactic acidosis contraindication 91273001 DOID:3650
Steatosis of liver contraindication 197321007
Toxic nephropathy contraindication 236514003
Breastfeeding (mother) contraindication 413712001
Obesity contraindication 414916001 DOID:9970
Drug Resistance to Anti-retroviral Therapy contraindication




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 4.73 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
DNA polymerase alpha catalytic subunit Enzyme Ki 5.93 CHEMBL
Fibroblast growth factor receptor 1 Kinase EC50 4.26 CHEMBL
Prolyl endopeptidase FAP Enzyme IC50 7.02 CHEMBL
DNA polymerase subunit gamma-1 Enzyme Ki 6.01 CHEMBL
Protein P Polyprotein INHIBITOR CHEMBL CHEMBL
Capsid protein Structural EC50 7.08 CHEMBL

External reference:

IDSource
4021357 VUID
N0000179520 NUI
141400 RXNORM
C0540694 UMLSCUI
CHEBI:31175 CHEBI
CHEMBL922 ChEMBL_ID
DB00718 DRUGBANK_ID
C106812 MESH_SUPPLEMENTAL_RECORD_UI
U6Q8Z01514 UNII
60871 PUBCHEM_CID
DB13868 DRUGBANK_ID
16958 MMSL
205746 MMSL
44701 MMSL
d04814 MMSL
C0050175 UMLSCUI
CHEMBL484 ChEMBL_ID
106941-25-7 SECONDARY_CAS_RN
60172 PUBCHEM_CID
7313 INN_ID
4021357 VANDF
4024286 VANDF
C053001 MESH_SUPPLEMENTAL_RECORD_UI
6GQP90I798 UNII
009376 NDDF
009377 NDDF
409114008 SNOMEDCT_US
412072006 SNOMEDCT_US
412073001 SNOMEDCT_US
CHEBI:2469 CHEBI
6GQP90I798 INXIGHT DRUGS
U6Q8Z01514 INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
ADEFOVIR DIPIVOXIL HUMAN PRESCRIPTION DRUG LABEL 1 42794-003 TABLET 10 mg ORAL ANDA 29 sections
Hepsera HUMAN PRESCRIPTION DRUG LABEL 1 46014-0501 TABLET 10 mg ORAL NDA 32 sections
Adefovir dipivoxil HUMAN PRESCRIPTION DRUG LABEL 1 60505-3947 TABLET 10 mg ORAL ANDA 29 sections