Orlistat

Identification

Summary

Orlistat is a reversible inhibitor of gastrointestinal lipases indicated for weight loss and weight maintenance.

Brand Names
Alli, Xenical
Generic Name
Orlistat
DrugBank Accession Number
DB01083
Background

The global prevalence of obesity is increasing rapidly. Obesity-related complications lead to significant personal and economic burden by reducing quality of life and increasing the cost of healthcare. In some individuals, diet and exercise are insufficient to maintain weight loss, and pharmacological or surgical intervention is required.14

Orlistat is a lipase inhibitor used in the treatment of obesity that works by inhibiting fat-metabolizing enzymes. It was approved by the FDA for use in combination with a reduced-calorie diet in 1999.15 This drug is a generally well-tolerated and effective weight-loss aid and is now available in both over-the-counter16 and prescription preparations, depending on the dosage quantity.15

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 495.7348
Monoisotopic: 495.392373811
Chemical Formula
C29H53NO5
Synonyms
  • (-)-Tetrahydrolipstatin
  • Orlipastat
  • Orlipastatum
  • Orlistat
  • Tetrahydrolipstatin
External IDs
  • RO 18-0647/002
  • RO-18-0647/002
  • RO-180647-002
  • RO-180647002

Pharmacology

Indication

Orlistat is indicated for obesity management including weight loss and weight maintenance when used in combination with calorie reduction in overweight and obese adults; this indication applies to both the prescription formulation of 120 mg15 and the over the counter formulation of 60 mg.16 Orlistat in the 120 mg prescription formulation is also indicated to reduce the risk for weight regain following weight loss.15

Pharmacology
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Associated Conditions
Associated Therapies
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Orlistat helps with weight reduction and maintenance by inhibiting the absorption of dietary fats via the inhibition of lipase enzymes.9,10

Mechanism of action

Orlistat is a potent and selective inhibitor of various lipase enzymes responsible for the metabolism of fat. It acts in the gastrointestinal (GI) tract via covalent binding to the serine residues located on the active site of both gastric and pancreatic lipase. When orlistat is taken with food containing fat, it partially inhibits the hydrolysis of triglycerides. This decreases absorption of monoaclglycerides and free fatty acids, contributing to weight maintenance and weight loss.12,15

TargetActionsOrganism
APancreatic triacylglycerol lipase
inhibitor
Humans
AGastric triacylglycerol lipase
inhibitor
Humans
UFatty acid synthase
inhibitor
Humans
Absorption

The systemic absorption and exposure of orlistat is low, however, systemic absorption of the drug is not required for orlistat activity.18 After an oral dose with 360 mg of radiolabeled orlistat, plasma radioactivity achieved a peak at about 8 hours. Plasma concentrations of unchanged parent drug were close to the lower end of detection limits (<5 ng/mL). In plasma samples of patients taking orlistat, the detection of unchanged drug was sporadic and very low concentrations were detected (<10 ng/mL or 0.02 μM) with no evidence suggesting drug accumulation.15

Volume of distribution

Volume of distribution cannot be obtained because the absorption of orlistat is minimal. Orlistat is minimally distributed to erythrocytes and is primarily bound to proteins.15

Protein binding

Orlistat is >99% bound to plasma proteins (mainly lipoproteins and albumin).15

Metabolism

Orlistat is hydrolyzed in the intestinal wall.17 In a radiolabeled orlistat mass balance study in obese patients, two metabolites were identified. The first metabolite, M1, was the hydrolyzed β-lactone ring product of orlistat. The second metabolite, M3, was produced from M1’s cleavage of the N-formyl leucine side-chain. Both metabolites accounted for about 42% of total plasma radioactivity. Both M1 and M3 are considered pharmacologically inactive.13,15

Route of elimination

After single oral dose of radiolabled orlistat in both normal weight and obese volunteers fecal excretion of the unabsorbed drug was found to be the major route of elimination with <2% urinary excretion.11,20 Fecal elimination of orlistat is estimated between 95-97%.15 Complete excretion by both routes occurs within in 3 to 5 days.20

Half-life

The half-life of orlistat of the small amount of absorbed orlistat ranges between 1-2 hours.13,15

Clearance

Not Available

Adverse Effects
Adverseeffects
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Toxicity

The oral LD50 of orlistat is >5000 mg/kg in rats.21 Single orlistat doses of 800 mg and multiple doses of up to 400 mg three times a day for 15 days have been administered to healthy weight and obese subjects without clinically significant adverse findings. In addition, doses of 240 mg three times a day have been given to obese patients for 6 months without a significant adverse effects. Post-marketing reports of overdoses cases indicate no adverse events or adverse events that are similar to those reported with the recommended dose. If a significant overdose with orlistat occurs, the patient should be observed for at least 24 hours. Based on the results of clinical studies, systemic effects caused by orlistat are likely to be rapidly reversible.20

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AcenocoumarolOrlistat may increase the anticoagulant activities of Acenocoumarol.
AcetazolamideOrlistat can cause a decrease in the absorption of Acetazolamide resulting in a reduced serum concentration and potentially a decrease in efficacy.
AlfacalcidolOrlistat can cause a decrease in the absorption of Alfacalcidol resulting in a reduced serum concentration and potentially a decrease in efficacy.
AlitretinoinOrlistat can cause a decrease in the absorption of Alitretinoin resulting in a reduced serum concentration and potentially a decrease in efficacy.
alpha-Tocopherol acetateOrlistat can cause a decrease in the absorption of alpha-Tocopherol acetate resulting in a reduced serum concentration and potentially a decrease in efficacy.
alpha-Tocopherol succinateOrlistat can cause a decrease in the absorption of alpha-Tocopherol succinate resulting in a reduced serum concentration and potentially a decrease in efficacy.
AmiodaroneOrlistat can cause a decrease in the absorption of Amiodarone resulting in a reduced serum concentration and potentially a decrease in efficacy.
AmobarbitalOrlistat can cause a decrease in the absorption of Amobarbital resulting in a reduced serum concentration and potentially a decrease in efficacy.
Beta caroteneOrlistat can cause a decrease in the absorption of Beta carotene resulting in a reduced serum concentration and potentially a decrease in efficacy.
BrexanoloneOrlistat can cause a decrease in the absorption of Brexanolone resulting in a reduced serum concentration and potentially a decrease in efficacy.
Interactions
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Food Interactions
  • Take with food. Take with meals or up to 1 hour after a meal. Doses may be skipped for missed meals or fat-free meals.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AlliTablet, chewable27 mgOralGlaxo Smith Kline (Ireland) Limited2016-09-082020-09-03EU flag
AlliCapsule60 mgOralGlaxo Smith Kline (Ireland) Limited2016-09-08Not applicableEU flag
AlliTablet, chewable27 mgOralGlaxo Smith Kline (Ireland) Limited2016-09-082020-09-03EU flag
AlliCapsule60 mgOralGlaxo Smith Kline (Ireland) Limited2016-09-08Not applicableEU flag
AlliTablet, chewable27 mgOralGlaxo Smith Kline (Ireland) Limited2016-09-082020-09-03EU flag
AlliCapsule60 mgOralGlaxo Smith Kline (Ireland) Limited2016-09-08Not applicableEU flag
AlliCapsule60 mgOralGlaxo Smith Kline (Ireland) Limited2016-09-08Not applicableEU flag
AlliTablet, chewable27 mgOralGlaxo Smith Kline (Ireland) Limited2016-09-082020-09-03EU flag
AlliTablet, chewable27 mgOralGlaxo Smith Kline (Ireland) Limited2016-09-082020-09-03EU flag
AlliCapsule60 mgOralGlaxo Smith Kline (Ireland) Limited2016-09-08Not applicableEU flag
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AlliCapsule60 mg/1OralGlaxoSmithKline Consumer Healthcare Holdings (US) LLC2007-02-07Not applicableUS flag
Alli capsule 60mgCapsule60 mgOralGSK CONSUMER HEALTHCARE SINGAPORE PTE. LTD.2010-04-07Not applicable
OBELIT 120 CAPSULE 120MGCapsule, gelatin coated120.00 mgOralACCORD HEALTHCARE PRIVATE LIMITED2017-08-04Not applicable
XENICAL CAPSULE 120MGCapsule120 MGOralDKSH SINGAPORE PTE. LTD.2005-01-31Not applicable

Categories

ATC Codes
A08AB01 — Orlistat
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as leucine and derivatives. These are compounds containing leucine or a derivative thereof resulting from reaction of leucine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Leucine and derivatives
Alternative Parents
Alpha amino acid esters / N-formyl-alpha amino acids / Fatty acid esters / Dicarboxylic acids and derivatives / Beta propiolactones / Secondary carboxylic acid amides / Oxetanes / Carboxylic acid esters / Oxacyclic compounds / Organopnictogen compounds
show 4 more
Substituents
Aliphatic heteromonocyclic compound / Alpha-amino acid ester / Beta_propiolactone / Carbonyl group / Carboxamide group / Carboxylic acid ester / Dicarboxylic acid or derivatives / Fatty acid ester / Fatty acyl / Hydrocarbon derivative
show 14 more
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals
  • Rat
  • Mouse

Chemical Identifiers

UNII
95M8R751W8
CAS number
96829-58-2
InChI Key
AHLBNYSZXLDEJQ-FWEHEUNISA-N
InChI
InChI=1S/C29H53NO5/c1-5-7-9-11-12-13-14-15-16-18-24(34-29(33)26(30-22-31)20-23(3)4)21-27-25(28(32)35-27)19-17-10-8-6-2/h22-27H,5-21H2,1-4H3,(H,30,31)/t24-,25-,26-,27-/m0/s1
IUPAC Name
(2S)-1-[(2S,3S)-3-hexyl-4-oxooxetan-2-yl]tridecan-2-yl (2S)-2-formamido-4-methylpentanoate
SMILES
CCCCCCCCCCC[C@@H](C[C@@H]1OC(=O)[C@H]1CCCCCC)OC(=O)[C@H](CC(C)C)NC=O

References

Synthesis Reference

Vilmos Keri, "Preparation of orlistat and orlistat crystalline forms." U.S. Patent US20030149095, issued August 07, 2003.

US20030149095
General References
  1. Torgerson JS, Hauptman J, Boldrin MN, Sjostrom L: XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care. 2004 Jan;27(1):155-61. [Article]
  2. Mancini MC, Halpern A: Pharmacological treatment of obesity. Arq Bras Endocrinol Metabol. 2006 Apr;50(2):377-89. Epub 2006 May 23. [Article]
  3. Menendez JA, Vellon L, Lupu R: Antitumoral actions of the anti-obesity drug orlistat (XenicalTM) in breast cancer cells: blockade of cell cycle progression, promotion of apoptotic cell death and PEA3-mediated transcriptional repression of Her2/neu (erbB-2) oncogene. Ann Oncol. 2005 Aug;16(8):1253-67. Epub 2005 May 3. [Article]
  4. Garcia SB, Barros LT, Turatti A, Martinello F, Modiano P, Ribeiro-Silva A, Vespucio MV, Uyemura SA: The anti-obesity agent Orlistat is associated to increase in colonic preneoplastic markers in rats treated with a chemical carcinogen. Cancer Lett. 2006 Aug 28;240(2):221-4. Epub 2005 Dec 27. [Article]
  5. Drew BS, Dixon AF, Dixon JB: Obesity management: update on orlistat. Vasc Health Risk Manag. 2007;3(6):817-21. [Article]
  6. Wong NN, Cheng-Lai A: Orlistat. Heart Dis. 2000 Mar-Apr;2(2):174-81. [Article]
  7. Hvizdos KM, Markham A: Orlistat: a review of its use in the management of obesity. Drugs. 1999 Oct;58(4):743-60. [Article]
  8. Lucas KH, Kaplan-Machlis B: Orlistat--a novel weight loss therapy. Ann Pharmacother. 2001 Mar;35(3):314-28. [Article]
  9. Curran MP, Scott LJ: Orlistat: a review of its use in the management of patients with obesity. Drugs. 2004;64(24):2845-64. [Article]
  10. Ballinger A, Peikin SR: Orlistat: its current status as an anti-obesity drug. Eur J Pharmacol. 2002 Apr 12;440(2-3):109-17. [Article]
  11. Zhi J, Melia AT, Eggers H, Joly R, Patel IH: Review of limited systemic absorption of orlistat, a lipase inhibitor, in healthy human volunteers. J Clin Pharmacol. 1995 Nov;35(11):1103-8. doi: 10.1002/j.1552-4604.1995.tb04034.x. [Article]
  12. Guerciolini R: Mode of action of orlistat. Int J Obes Relat Metab Disord. 1997 Jun;21 Suppl 3:S12-23. [Article]
  13. Zhi J, Melia AT, Funk C, Viger-Chougnet A, Hopfgartner G, Lausecker B, Wang K, Fulton JS, Gabriel L, Mulligan TE: Metabolic profiles of minimally absorbed orlistat in obese/overweight volunteers. J Clin Pharmacol. 1996 Nov;36(11):1006-11. doi: 10.1177/009127009603601104. [Article]
  14. Williams DM, Nawaz A, Evans M: Drug Therapy in Obesity: A Review of Current and Emerging Treatments. Diabetes Ther. 2020 Jun;11(6):1199-1216. doi: 10.1007/s13300-020-00816-y. Epub 2020 Apr 15. [Article]
  15. FDA Approved Drug Products: Xenical (orlistat) capsules [Link]
  16. FDA Approved Drug Products: ALLI (orlistat) oral capsules OTC [Link]
  17. FDA: Orlistat (marketed as Alli and Xenical) Information [Link]
  18. NIH StatPearls: Orlistat [Link]
  19. DailyMed: Alli (orlistat) oral capsule [Link]
  20. Product monograph: Xenical (orlistat) oral capsules [Link]
  21. Fagron MSDS: Orlistat [Link]
Human Metabolome Database
HMDB0015215
PubChem Compound
3034010
PubChem Substance
46508309
ChemSpider
2298564
BindingDB
24567
RxNav
37925
ChEBI
94686
ChEMBL
CHEMBL175247
ZINC
ZINC000008214635
Therapeutic Targets Database
DAP000053
PharmGKB
PA164776864
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Orlistat
FDA label
Download (82.5 KB)
MSDS
Download (114 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentType II Diabetes in Subjects BMI 27 to 321
4CompletedTreatment1. Obesity1
4CompletedTreatmentBMI >27 kg/m2 / Obesity (Disorder)1
4CompletedTreatmentCardiovascular Disease (CVD) / Obesity (Disorder)1
4CompletedTreatmentEating, Binge / Obesity (Disorder)1
4CompletedTreatmentFatty Liver / Hepatitis1
4CompletedTreatmentFatty Liver / Hepatitis C Virus (HCV) Infection1
4CompletedTreatmentObesity (Disorder)2
4RecruitingTreatmentObesity (Disorder) / Type 2 Diabetes Mellitus1
4TerminatedTreatmentGastric Banding / Type 2 Diabetes Mellitus1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • A-S Medication Solutions LLC
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • F Hoffmann La Roche Ltd.
  • F Hoffmann-La Roche Ltd.
  • GlaxoSmithKline Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Nucare Pharmaceuticals Inc.
  • Physicians Total Care Inc.
  • Southwood Pharmaceuticals
Dosage Forms
FormRouteStrength
CapsuleOral60 MG
CapsuleOral60 mg/1
TabletOral27 MG
Tablet, chewableOral27 mg
TabletOral
Capsule, coatedOral60 mg
Capsule, coatedOral120 mg
Capsule, gelatin coatedOral120.00 mg
CapsuleOral
PowderNot applicable1 kg/1kg
Capsule, liquid filledOral120 mg
Capsule, liquid filledOral60 mg
CapsuleOral120 mg/1
Capsule, gelatin coatedOral120 mg
Capsule, coatedOral50 %
Tablet, solubleOral120 mg
CapsuleOral120 mg
Prices
Unit descriptionCostUnit
Xenical 120 mg capsule4.44USD capsule
Alli 60 mg capsule0.67USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US4598089No1986-07-012009-12-18US flag
CA2383036No2006-01-102020-09-11Canada flag
CA2258095No2000-02-222018-01-24Canada flag
US6004996Yes1999-12-212018-07-06US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)40-50https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6223334/
boiling point (°C)616https://www.chemicalbook.com/ChemicalProductProperty_US_CB2431985.aspx
logP4.4https://www.rochecanada.com/PMs/Xenical/Xenical_PM_E.pdf
pKa15https://www.chemicalbook.com/ChemicalProductProperty_US_CB2431985.aspx
Predicted Properties
PropertyValueSource
Water Solubility9.19e-05 mg/mLALOGPS
logP7.61ALOGPS
logP8.11ChemAxon
logS-6.7ALOGPS
pKa (Strongest Acidic)12.74ChemAxon
pKa (Strongest Basic)-0.91ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area81.7 Å2ChemAxon
Rotatable Bond Count23ChemAxon
Refractivity139.94 m3·mol-1ChemAxon
Polarizability61.12 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9728
Blood Brain Barrier+0.5923
Caco-2 permeable-0.5611
P-glycoprotein substrateSubstrate0.5411
P-glycoprotein inhibitor IInhibitor0.6242
P-glycoprotein inhibitor IIInhibitor0.5301
Renal organic cation transporterNon-inhibitor0.9097
CYP450 2C9 substrateNon-substrate0.854
CYP450 2D6 substrateNon-substrate0.826
CYP450 3A4 substrateSubstrate0.5867
CYP450 1A2 substrateNon-inhibitor0.8458
CYP450 2C9 inhibitorNon-inhibitor0.8305
CYP450 2D6 inhibitorNon-inhibitor0.8869
CYP450 2C19 inhibitorNon-inhibitor0.7315
CYP450 3A4 inhibitorNon-inhibitor0.8308
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.907
Ames testNon AMES toxic0.7333
CarcinogenicityNon-carcinogens0.8628
BiodegradationNot ready biodegradable0.7808
Rat acute toxicity2.3363 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9671
hERG inhibition (predictor II)Non-inhibitor0.9395
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Triglyceride lipase activity
Specific Function
Not Available
Gene Name
PNLIP
Uniprot ID
P16233
Uniprot Name
Pancreatic triacylglycerol lipase
Molecular Weight
51156.48 Da
References
  1. Uusitupa M: New aspects in the management of obesity: operation and the impact of lipase inhibitors. Curr Opin Lipidol. 1999 Feb;10(1):3-7. [Article]
  2. Leonhardt M, Hrupka B, Langhans W: New approaches in the pharmacological treatment of obesity. Eur J Nutr. 1999 Feb;38(1):1-13. [Article]
  3. Bray GA: Drug treatment of obesity. Baillieres Best Pract Res Clin Endocrinol Metab. 1999 Apr;13(1):131-48. [Article]
  4. Bray GA: A concise review on the therapeutics of obesity. Nutrition. 2000 Oct;16(10):953-60. [Article]
  5. Gomis Barbara R: [Pharmacological treatment of obesity]. Rev Med Univ Navarra. 2004 Apr-Jun;48(2):63-5. [Article]
  6. Drew BS, Dixon AF, Dixon JB: Obesity management: update on orlistat. Vasc Health Risk Manag. 2007;3(6):817-21. [Article]
  7. Wong NN, Cheng-Lai A: Orlistat. Heart Dis. 2000 Mar-Apr;2(2):174-81. [Article]
  8. Nelson RH, Miles JM: The use of orlistat in the treatment of obesity, dyslipidaemia and Type 2 diabetes. Expert Opin Pharmacother. 2005 Nov;6(14):2483-91. [Article]
  9. Heck AM, Yanovski JA, Calis KA: Orlistat, a new lipase inhibitor for the management of obesity. Pharmacotherapy. 2000 Mar;20(3):270-9. [Article]
  10. Henness S, Perry CM: Orlistat: a review of its use in the management of obesity. Drugs. 2006;66(12):1625-56. [Article]
  11. Ballinger A, Peikin SR: Orlistat: its current status as an anti-obesity drug. Eur J Pharmacol. 2002 Apr 12;440(2-3):109-17. [Article]
  12. McNeely W, Benfield P: Orlistat. Drugs. 1998 Aug;56(2):241-9; discussion 250. [Article]
  13. FDA Approved Drug Products: Xenical (orlistat) capsules [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Triglyceride lipase activity
Specific Function
Not Available
Gene Name
LIPF
Uniprot ID
P07098
Uniprot Name
Gastric triacylglycerol lipase
Molecular Weight
45237.375 Da
References
  1. Lunagariya NA, Patel NK, Jagtap SC, Bhutani KK: Inhibitors of pancreatic lipase: state of the art and clinical perspectives. EXCLI J. 2014 Aug 22;13:897-921. eCollection 2014. [Article]
  2. Sternby B, Hartmann D, Borgstrom B, Nilsson A: Degree of in vivo inhibition of human gastric and pancreatic lipases by Orlistat (Tetrahydrolipstatin, THL) in the stomach and small intestine. Clin Nutr. 2002 Oct;21(5):395-402. doi: 10.1054/clnu.2002.0565. [Article]
  3. Heck AM, Yanovski JA, Calis KA: Orlistat, a new lipase inhibitor for the management of obesity. Pharmacotherapy. 2000 Mar;20(3):270-9. [Article]
Details
3. Fatty acid synthase
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Poly(a) rna binding
Specific Function
Fatty acid synthetase catalyzes the formation of long-chain fatty acids from acetyl-CoA, malonyl-CoA and NADPH. This multifunctional protein has 7 catalytic activities and an acyl carrier protein.
Gene Name
FASN
Uniprot ID
P49327
Uniprot Name
Fatty acid synthase
Molecular Weight
273424.06 Da
References
  1. Kridel SJ, Axelrod F, Rozenkrantz N, Smith JW: Orlistat is a novel inhibitor of fatty acid synthase with antitumor activity. Cancer Res. 2004 Mar 15;64(6):2070-5. [Article]
  2. Dowling S, Cox J, Cenedella RJ: Inhibition of fatty acid synthase by Orlistat accelerates gastric tumor cell apoptosis in culture and increases survival rates in gastric tumor bearing mice in vivo. Lipids. 2009 Jun;44(6):489-98. doi: 10.1007/s11745-009-3298-2. Epub 2009 Apr 21. [Article]
  3. Pemble CW 4th, Johnson LC, Kridel SJ, Lowther WT: Crystal structure of the thioesterase domain of human fatty acid synthase inhibited by Orlistat. Nat Struct Mol Biol. 2007 Aug;14(8):704-9. Epub 2007 Jul 8. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
Curator comments
Supported by limited in vitro data only.
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Novotna A, Doricakova A, Vrzal R, Maurel P, Pavek P, Dvorak Z: Investigation of Orlistat effects on PXR activation and CYP3A4 expression in primary human hepatocytes and human intestinal LS174T cells. Eur J Pharm Sci. 2010 Oct 9;41(2):276-80. doi: 10.1016/j.ejps.2010.06.019. Epub 2010 Jul 3. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Phospholipase a2 activity
Specific Function
Selectively hydrolyzes arachidonyl phospholipids in the sn-2 position releasing arachidonic acid. Together with its lysophospholipid activity, it is implicated in the initiation of the inflammatory...
Gene Name
PLA2G4A
Uniprot ID
P47712
Uniprot Name
Cytosolic phospholipase A2
Molecular Weight
85238.2 Da
References
  1. Filippatos TD, Gazi IF, Liberopoulos EN, Athyros VG, Elisaf MS, Tselepis AD, Kiortsis DN: The effect of orlistat and fenofibrate, alone or in combination, on small dense LDL and lipoprotein-associated phospholipase A2 in obese patients with metabolic syndrome. Atherosclerosis. 2007 Aug;193(2):428-37. Epub 2006 Sep 5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Poly(a) rna binding
Specific Function
Fatty acid synthetase catalyzes the formation of long-chain fatty acids from acetyl-CoA, malonyl-CoA and NADPH. This multifunctional protein has 7 catalytic activities and an acyl carrier protein.
Gene Name
FASN
Uniprot ID
P49327
Uniprot Name
Fatty acid synthase
Molecular Weight
273424.06 Da
References
  1. Kridel SJ, Axelrod F, Rozenkrantz N, Smith JW: Orlistat is a novel inhibitor of fatty acid synthase with antitumor activity. Cancer Res. 2004 Mar 15;64(6):2070-5. [Article]
  2. Pemble CW 4th, Johnson LC, Kridel SJ, Lowther WT: Crystal structure of the thioesterase domain of human fatty acid synthase inhibited by Orlistat. Nat Struct Mol Biol. 2007 Aug;14(8):704-9. Epub 2007 Jul 8. [Article]
  3. Dowling S, Cox J, Cenedella RJ: Inhibition of fatty acid synthase by Orlistat accelerates gastric tumor cell apoptosis in culture and increases survival rates in gastric tumor bearing mice in vivo. Lipids. 2009 Jun;44(6):489-98. doi: 10.1007/s11745-009-3298-2. Epub 2009 Apr 21. [Article]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. FDA Approved Drug Products: Xenical (orlistat) capsules [Link]

Drug created on June 13, 2005 13:24 / Updated on October 22, 2021 23:18