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

Stem definitionDrug idCAS RN
diuretics, chlorothiazide derivatives 2733 133-67-5

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • triclormetiazide
  • trichlormethiazide
  • hydrotrichlorothiazide
  • trichlormetazid
  • trichlormethiazid
  • trichloromethiazide
A thiazide diuretic with properties similar to those of HYDROCHLOROTHIAZIDE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p830)
  • Molecular weight: 380.64
  • Formula: C8H8Cl3N3O4S2
  • CLOGP: 0.88
  • LIPINSKI: 0
  • HAC: 7
  • HDO: 3
  • TPSA: 118.36
  • ALOGS: -2.96
  • ROTB: 2
  • Status: OFM
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
4 mg O
4 mg O

ADMET properties:

PropertyValueReference
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.18 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 60 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
S (Water solubility) 0.80 mg/mL Bocci G, Oprea TI, Benet LZ
BDDCS (Biopharmaceutical Drug Disposition Classification System) 3 Bocci G, Oprea TI, Benet LZ

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 0.496 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 40.365 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 0.612 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 1.581 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 23.030 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 28.150 % High 1
herg hERG pIC50 3.911 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 1.146 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 3.365 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 13.040 % High 1
kinase-safety-class ACVR2A,ACVR2B,AURKA,AXL,BRAF,BTK,CAMK2D,CDK5,CDK9,DDR1,DYRK1B,EGFR,EIF2AK3,EPHB4,ERBB2,GRK2,GSK3B,ITK,JAK2,JAK3,MAP2K6,MAP3K7,MAPK10,MAPK7,MAPK9,MAPKAPK2,NTRK2,PDK1,PDK2,PDK4,PDPK1,PIK3CA,PIK3CB,PIK3CD,PIK3CG,PIM2,PRKDC,SIK2,STK33,SYK,TEK,TGFBR1,TTK,ZAP70 44
kinase-selectivity-class AXL,GRK2,MAP2K6,PDK1,PDK2,TEK,ZAP70 7
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 2.483 High 1
mh-clint Mouse hepatocyte intrinsic clearance 19.588 High 1
mppb Mouse plasma protein binding (% unbound) 20.300 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 3.681 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 20.260 % High 1
rh-clint Rat hepatocyte intrinsic clearance 10.990 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 91.690 % High 1
rppb Rat plasma protein binding (% unbound) 17.510 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 383.707 uM High 1

Approvals:

DateAgencyCompanyOrphan
March 9, 1960 FDA

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
Vital capacity decreased 360.73 35.69 61 2994 1758 90623634
Reversible airways obstruction 355.47 35.69 61 2994 1922 90623470
Sputum culture positive 347.69 35.69 61 2994 2192 90623200
Bronchial secretion retention 318.90 35.69 61 2994 3554 90621838
Eosinophil count increased 245.72 35.69 62 2993 13019 90612373
Upper-airway cough syndrome 231.93 35.69 61 2994 15074 90610318
Multiple allergies 231.88 35.69 61 2994 15085 90610307
Obstructive airways disorder 212.46 35.69 64 2991 25805 90599587
Pulmonary mass 193.19 35.69 61 2994 28711 90596681
Full blood count abnormal 178.78 35.69 61 2994 36536 90588856
Respiratory tract infection 150.31 35.69 61 2994 59017 90566375
Renal impairment 94.18 35.69 53 3002 105368 90520024
Sputum culture 78.71 35.69 13 3042 321 90625071
Cardiac failure 74.03 35.69 46 3009 109450 90515942
Pneumonia 67.02 35.69 94 2961 637965 89987427
Cough 63.93 35.69 70 2985 368892 90256500

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
Renal impairment 99.22 22.43 70 2624 110158 42508483
Cardiac failure 89.57 22.43 65 2629 106791 42511850
Hepatic function abnormal 53.93 22.43 36 2658 51531 42567110
Interstitial lung disease 52.94 22.43 42 2652 78420 42540221
Cerebral infarction 48.41 22.43 28 2666 31141 42587500
Cardiac failure chronic 43.68 22.43 18 2676 9583 42609058
Shoshin beriberi 43.22 22.43 7 2687 78 42618563
Decreased appetite 35.86 22.43 52 2642 193085 42425556
Hyperuricaemia 27.70 22.43 13 2681 9411 42609230
Vitamin B1 deficiency 26.59 22.43 6 2688 412 42618229
Drug ineffective 22.69 22.43 6 2688 630191 41988450
Renal ischaemia 22.48 22.43 7 2687 1663 42616978

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
Vital capacity decreased 317.72 23.92 60 5886 2013 110581340
Reversible airways obstruction 306.53 23.92 60 5886 2439 110580914
Sputum culture positive 280.07 23.92 60 5886 3829 110579524
Bronchial secretion retention 264.77 23.92 60 5886 4964 110578389
Multiple allergies 211.61 23.92 60 5886 12203 110571150
Upper-airway cough syndrome 200.65 23.92 61 5885 15796 110567557
Eosinophil count increased 191.65 23.92 63 5883 20995 110562358
Renal impairment 185.28 23.92 119 5827 188326 110395027
Cardiac failure 163.74 23.92 110 5836 187516 110395837
Pulmonary mass 159.96 23.92 64 5882 37237 110546116
Obstructive airways disorder 150.08 23.92 65 5881 46084 110537269
Respiratory tract infection 122.87 23.92 65 5881 71552 110511801
Full blood count abnormal 122.76 23.92 60 5886 55992 110527361
Hepatic function abnormal 81.69 23.92 54 5892 89241 110494112
Cerebral infarction 72.14 23.92 41 5905 51797 110531556
Sputum culture 66.83 23.92 12 5934 302 110583051
Interstitial lung disease 66.37 23.92 57 5889 139277 110444076
Pneumonia 59.17 23.92 139 5807 876575 109706778
Cardiac failure chronic 53.33 23.92 22 5924 13789 110569564
Hyperuricaemia 45.66 23.92 20 5926 14511 110568842
Shoshin beriberi 44.35 23.92 7 5939 78 110583275
Blood pressure decreased 40.94 23.92 40 5906 115051 110468302
Decreased appetite 38.19 23.92 81 5865 475765 110107588
Fatigue 35.02 23.92 11 5935 1215947 109367406
Right ventricular failure 34.68 23.92 20 5926 25934 110557419
Dehydration 32.83 23.92 56 5890 279455 110303898
Vitamin B1 deficiency 32.32 23.92 8 5938 962 110582391
Platelet count decreased 32.27 23.92 50 5896 230393 110352960
Upper respiratory tract inflammation 31.55 23.92 11 5935 4360 110578993
Pulmonary arterial hypertension 30.49 23.92 20 5926 32548 110550805
Cough 29.69 23.92 72 5874 461569 110121784
Uraemic encephalopathy 28.59 23.92 7 5939 805 110582548
Concomitant disease aggravated 28.44 23.92 15 5931 16349 110567004
Brain natriuretic peptide increased 27.54 23.92 13 5933 11196 110572157
Hyperkalaemia 24.14 23.92 33 5913 135763 110447590

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC C03AA06 CARDIOVASCULAR SYSTEM
DIURETICS
LOW-CEILING DIURETICS, THIAZIDES
Thiazides, plain
ATC C03AB06 CARDIOVASCULAR SYSTEM
DIURETICS
LOW-CEILING DIURETICS, THIAZIDES
Thiazides and potassium in combination
ATC C03EA02 CARDIOVASCULAR SYSTEM
DIURETICS
DIURETICS AND POTASSIUM-SPARING AGENTS IN COMBINATION
Low-ceiling diuretics and potassium-sparing agents
MeSH PA D000959 Antihypertensive Agents
MeSH PA D002317 Cardiovascular Agents
MeSH PA D004232 Diuretics
MeSH PA D045283 Natriuretic Agents
MeSH PA D049990 Membrane Transport Modulators
MeSH PA D049993 Sodium Chloride Symporter Inhibitors
CHEBI has role CHEBI:35498 diuretic
CHEBI has role CHEBI:35554 cardiovascular drug
CHEBI has role CHEBI:35674 antihypertensive agent

Related Drugs by ATC class:

C03AA Thiazides, plain 9 drugs
bendroflumethiazidechlorothiazidecyclopenthiazidecyclothiazidehydrochlorothiazidehydroflumethiazidemebutizidemethylclothiazidepolythiazide
C03AB Thiazides and potassium in combination 8 drugs
bendroflumethiazidechlorothiazidecyclopenthiazidecyclothiazidehydrochlorothiazidehydroflumethiazidemethylclothiazidepolythiazide
C03EA Low-ceiling diuretics and potassium-sparing agents 9 drugs
altizidebendroflumethiazidebutizidechlortalidonecyclopenthiazideepitizidehydrochlorothiazidemebutizidemetolazone

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

DiseaseRelationSNOMED_IDDOID
Hypertensive disorder indication 38341003 DOID:10763
Suicidal thoughts contraindication 6471006
Peptic ulcer contraindication 13200003 DOID:750
Chronic disease of respiratory system contraindication 17097001
Electroconvulsive therapy contraindication 23835007
Depressive disorder contraindication 35489007
Conduction disorder of the heart contraindication 44808001
Chronic heart failure contraindication 48447003
Ulcerative colitis contraindication 64766004 DOID:8577
Epilepsy contraindication 84757009 DOID:1826
Kidney disease contraindication 90708001 DOID:557
Calculus in biliary tract contraindication 266474003




🐶 Veterinary Drug Use

SpeciesUseRelation
Cattle No Use Class Stated Or Implied Indication

🐶 Veterinary products

ProductApplicantIngredients
Naquasone Bolus Intervet Inc. 2

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 7.05 acidic
pKa2 10.3 acidic
pKa3 1.29 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
Solute carrier family 12 member 3 Transporter INHIBITOR A2 7 WOMBAT-PK CHEMBL
Carbonic anhydrase 2 Enzyme Ki 7.04 CHEMBL
Carbonic anhydrase 1 Enzyme Ki 6.46 CHEMBL
Carbonic anhydrase 9 Enzyme Ki 7.06 CHEMBL
Carbonic anhydrase 12 Enzyme Ki 6.51 CHEMBL
Carbonic anhydrase 5A, mitochondrial Enzyme Ki 6.12 CHEMBL
Carbonic anhydrase 5B, mitochondrial Enzyme Ki 6.87 CHEMBL
Carbonic anhydrase 7 Enzyme Ki 8.10 CHEMBL
Carbonic anhydrase 6 Enzyme Ki 5.61 CHEMBL
Carbonic anhydrase 14 Enzyme Ki 5.46 CHEMBL
Carbonic anhydrase 4 Enzyme Ki 6.35 CHEMBL
Carbonic anhydrase 13 Enzyme Ki 6.19 CHEMBL

External reference:

IDSource
4018612 VUID
N0000146925 NUI
D00658 KEGG_DRUG
4018612 VANDF
C0040899 UMLSCUI
CHEBI:9683 CHEBI
CHEMBL1054 ChEMBL_ID
DB01021 DRUGBANK_ID
D014237 MESH_DESCRIPTOR_UI
5560 PUBCHEM_CID
7314 IUPHAR_LIGAND_ID
1012 INN_ID
Q58C92TUN0 UNII
10772 RXNORM
3169 MMSL
5619 MMSL
d00646 MMSL
002300 NDDF
11473005 SNOMEDCT_US
409112007 SNOMEDCT_US
Q58C92TUN0 INXIGHT DRUGS

Pharmaceutical products:

None