orlistat Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
gastrointestinal lipase inhibitors 1996 96829-58-2

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • orlistat
  • tetrahydrolipstatin
  • xenical
  • alli
  • tetrahydrolipastatin
A lactone derivative of LEUCINE that acts as a pancreatic lipase inhibitor to limit the absorption of dietary fat; it is used in the management of obesity.
  • Molecular weight: 495.75
  • Formula: C29H53NO5
  • CLOGP: 8.61
  • LIPINSKI: 1
  • HAC: 6
  • HDO: 1
  • TPSA: 81.70
  • ALOGS: -6.73
  • ROTB: 23
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.36 g O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 4 Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 1 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 9.22 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 1 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H

Approvals:

DateAgencyCompanyOrphan
April 23, 1999 FDA HOFFMANN LA ROCHE

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
Steatorrhoea 173.50 19.39 31 4930 369 46680732
Cerebral venous thrombosis 92.94 19.39 25 4936 2102 46678999
Thalamic infarction 68.43 19.39 15 4946 530 46680571
Drug interaction 63.48 19.39 92 4869 203002 46478099
Cholelithiasis 55.26 19.39 40 4921 38641 46642460
Rectal discharge 54.61 19.39 12 4949 429 46680672
Rectal haemorrhage 53.37 19.39 39 4922 38216 46642885
Abdominal pain 49.58 19.39 88 4873 229943 46451158
Crystal nephropathy 42.25 19.39 11 4950 814 46680287
Haematochezia 38.73 19.39 32 4929 37461 46643640
Hyperoxaluria 36.83 19.39 7 4954 119 46680982
Kidney fibrosis 36.30 19.39 11 4950 1414 46679687
Slow response to stimuli 32.70 19.39 9 4952 823 46680278
Nephropathy 32.34 19.39 14 4947 4991 46676110
Oxalosis 30.61 19.39 5 4956 33 46681068
Jaundice 30.58 19.39 25 4936 28820 46652281
Acute hepatic failure 30.04 19.39 19 4942 14702 46666399
Obesity 28.15 19.39 18 4943 14188 46666913
Abdominal pain upper 27.95 19.39 53 4908 145252 46535849
Urine oxalate increased 27.82 19.39 6 4955 196 46680905
Renal tubular atrophy 26.79 19.39 7 4954 525 46680576
Virologic failure 24.70 19.39 9 4952 2046 46679055
Oropharyngeal blistering 23.70 19.39 7 4954 825 46680276
Vanishing bile duct syndrome 20.64 19.39 6 4955 668 46680433
Bradyphrenia 20.59 19.39 11 4950 6219 46674882
Pregnancy on oral contraceptive 20.44 19.39 7 4954 1327 46679774

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
Nephropathy 44.77 25.39 14 1174 5402 29945888
Blood uric acid increased 43.31 25.39 14 1174 6009 29945281
Hyperoxaluria 29.07 25.39 5 1183 134 29951156
Sleep apnoea syndrome 26.31 25.39 13 1175 16844 29934446

Pharmacologic Action:

SourceCodeDescription
ATC A08AB01 ALIMENTARY TRACT AND METABOLISM
ANTIOBESITY PREPARATIONS, EXCL. DIET PRODUCTS
ANTIOBESITY PREPARATIONS, EXCL. DIET PRODUCTS
Peripherally acting antiobesity products
FDA MoA N0000009916 Lipase Inhibitors
FDA EPC N0000175591 Intestinal Lipase Inhibitor
MeSH PA D019440 Anti-Obesity Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D057847 Lipid Regulating Agents
CHEBI has role CHEBI:65001 pancreatic triacylglycerol lipase inhibitor
CHEBI has role CHEBI:71476 (fas) inhibitors
CHEBI has role CHEBI:74518 anti-obestic agent

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Obesity indication 414916001 DOID:9970
Primary hyperoxaluria contraindication 17901006 DOID:2977
Obstruction of bile duct contraindication 30144000
Anorexia nervosa contraindication 56882008 DOID:8689
Hepatic failure contraindication 59927004
Bulimia nervosa contraindication 78004001
Vitamin deficiency contraindication 85670002
Hepatic necrosis contraindication 87248009
Liver function tests abnormal contraindication 166603001
Drug-induced hepatitis contraindication 235876009
Malabsorption States contraindication
Calcium Oxalate Renal Calculi contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 13.77 acidic

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
Pancreatic triacylglycerol lipase Enzyme INHIBITOR IC50 8.90 IUPHAR DRUG LABEL
Gastric triacylglycerol lipase Enzyme INHIBITOR CHEMBL DRUG LABEL
Monoacylglycerol lipase ABHD12 Enzyme IC50 7.10 CHEMBL
Monoacylglycerol lipase ABHD6 Enzyme IC50 7.32 CHEMBL
Sn1-specific diacylglycerol lipase alpha Enzyme IC50 8 CHEMBL
Abhydrolase domain-containing protein 16A Enzyme IC50 7.52 CHEMBL
Platelet-activating factor acetylhydrolase Enzyme IC50 7.30 CHEMBL
Sn1-specific diacylglycerol lipase beta Enzyme IC50 7.22 CHEMBL
Cannabinoid receptor 1 GPCR Ki 5.60 CHEMBL
Fatty-acid amide hydrolase 1 Enzyme IC50 8 CHEMBL
Pancreatic triacylglycerol lipase Enzyme IC50 6.66 CHEMBL

External reference:

IDSource
4021159 VUID
N0000148610 NUI
D04028 KEGG_DRUG
4021159 VANDF
C1871879 UMLSCUI
CHEBI:94686 CHEBI
CHEMBL175247 ChEMBL_ID
D000077403 MESH_DESCRIPTOR_UI
3034010 PUBCHEM_CID
DB01083 DRUGBANK_ID
5277 IUPHAR_LIGAND_ID
6318 INN_ID
95M8R751W8 UNII
226918 RXNORM
109396 MMSL
29932 MMSL
8088 MMSL
d04429 MMSL
007654 NDDF
116093009 SNOMEDCT_US
387007000 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
ALLI HUMAN OTC DRUG LABEL 1 0135-0461 CAPSULE 60 mg ORAL NDA 17 sections
Xenical HUMAN PRESCRIPTION DRUG LABEL 1 61269-460 CAPSULE 120 mg ORAL NDA 31 sections