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Identification
NameBimatoprost
Accession NumberDB00905  (APRD00826, DB06863)
Typesmall molecule
Groupsapproved, investigational
Description

Bimatoprost ophthalmic solution is a topical medication used for controlling the progression of glaucoma or ocular hypertension, by reducing intraocular pressure. It is a prostaglandin analogue that works by increasing the outflow of aqueous fluid from the eyes. It binds to the prostanoid FP receptor.

Structure
Thumb
SynonymsNot Available
SaltsNot Available
Brand names
NameCompany
LumiganNot Available
Brand mixturesNot Available
Categories
CAS number155206-00-1
WeightAverage: 415.5656
Monoisotopic: 415.272258677
Chemical FormulaC25H37NO4
InChI KeyAQOKCDNYWBIDND-FTOWTWDKSA-N
InChI
InChI=1S/C25H37NO4/c1-2-26-25(30)13-9-4-3-8-12-21-22(24(29)18-23(21)28)17-16-20(27)15-14-19-10-6-5-7-11-19/h3,5-8,10-11,16-17,20-24,27-29H,2,4,9,12-15,18H2,1H3,(H,26,30)/b8-3-,17-16+/t20-,21+,22+,23-,24+/m0/s1
IUPAC Name
(5Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(1E,3S)-3-hydroxy-5-phenylpent-1-en-1-yl]cyclopentyl]-N-ethylhept-5-enamide
SMILES
CCNC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1\C=C\[C@@H](O)CCC1=CC=CC=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassLipids
ClassEicosanoids
SubclassProstaglandins and related compounds
Direct parentProstaglandins and related compounds
Alternative parentsN-acyl Amines; Benzene and Substituted Derivatives; Secondary Carboxylic Acid Amides; Secondary Alcohols; Cyclic Alcohols and Derivatives; Enolates; Carboxylic Acids; Polyamines
Substituentsn-acyl-amine; benzene; cyclic alcohol; secondary carboxylic acid amide; secondary alcohol; carboxamide group; carboxylic acid derivative; enolate; polyamine; carboxylic acid; amine; alcohol; organonitrogen compound
Classification descriptionThis compound belongs to the prostaglandins and related compounds. These are unsaturated carboxylic acids consisting of of a 20 carbon skeleton that also contains a five member ring, and are based upon the fatty acid arachidonic acid.
Pharmacology
IndicationFor the reduction of elevated intraocular pressure in patients with open angle glaucoma or ocular hypertension who are intolerant of other intraocular pressure lowering medications or insufficiently responsive (failed to achieve target IOP determined after multiple measurements over time) to another intraocular pressure lowering medication.
PharmacodynamicsBimatoprost is a prostamide, a synthetic structural analog of prostaglandin with ocular hypotensive activity, that is chemically related to prostamide F. It selectively mimics the effects of naturally occurring substances, prostamides. Bimatoprost lowers intraocular pressure (IOP) in humans. Elevated IOP presents a major risk factor for glaucomatous field loss. The higher the level of IOP, the greater the likelihood of optic nerve damage and visual field loss.
Mechanism of actionBimatoprost is believed to lower intraocular pressure (IOP) in humans by increasing outflow of aqueous humor through both the trabecular meshwork and uveoscleral routes. Bimatoprost reduces the pressure in the eye by mimicking the action of a naturally-occuring prostaglandin. Prostaglandins are a group of chemicals found in many places in the body. In the eye, they increase the drainage of the aqueous humour out of the eyeball. Bimatoprost is a synthetic compound related to one of the natural prostaglandins, and works by increasing the drainage of aqueous humour out of the eyeball. Bimatoprost may also lower the rate of aqueous formation in the eye. Both these effects decrease the pressure within the eye.
AbsorptionSystemically absorbed when administered to the eye.
Volume of distribution
  • 0.67 L/kg
Protein bindingApproximately 88% of bimatoprost is bound in human plasma.
Metabolism

Bimatoprost undergoes oxidation, N-deethylation and glucuronidation to form a variety of metabolites.

Route of eliminationUp to 67% of the administered dose was excreted in the urine while 25% of the dose was recovered in the feces.
Half lifeElimination half-life is approximately 45 minutes.
Clearance
  • 1.5 L/hr/kg [Healthy subjects receiving IV administration of 3.12 ug/kg]
ToxicityIn oral (by gavage) mouse and rat studies, doses up to 100 mg/kg/day did not produce any toxicity. This dose expressed as mg/m2 is at least 70 times higher than the accidental dose of one bottle of bimatoprost for a 10 kg child.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9975
Blood Brain Barrier + 0.825
Caco-2 permeable - 0.5699
P-glycoprotein substrate Substrate 0.5541
P-glycoprotein inhibitor I Non-inhibitor 0.8671
P-glycoprotein inhibitor II Non-inhibitor 0.8616
Renal organic cation transporter Non-inhibitor 0.8078
CYP450 2C9 substrate Non-substrate 0.7703
CYP450 2D6 substrate Non-substrate 0.7406
CYP450 3A4 substrate Substrate 0.552
CYP450 1A2 substrate Non-inhibitor 0.6764
CYP450 2C9 substrate Non-inhibitor 0.7695
CYP450 2D6 substrate Non-inhibitor 0.6384
CYP450 2C19 substrate Non-inhibitor 0.7632
CYP450 3A4 substrate Non-inhibitor 0.757
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7049
Ames test Non AMES toxic 0.7646
Carcinogenicity Non-carcinogens 0.9257
Biodegradation Not ready biodegradable 0.6415
Rat acute toxicity 2.1085 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9251
hERG inhibition (predictor II) Non-inhibitor 0.7822
Pharmacoeconomics
Manufacturers
  • Allergan inc
Packagers
Dosage forms
FormRouteStrength
SolutionOphthalmic
Prices
Unit descriptionCostUnit
Lumigan .03% 7.5ml Bottle279.56USDbottle
Lumigan .03% 5ml Bottle171.4USDbottle
Lumigan .03% 2.5ml Bottle91.16USDbottle
Lumigan 0.03% eye drops44.82USDml
Latisse 0.03% eyelash solution36.0USDml
Lumigan 0.03 % Solution12.18USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States73514042004-05-252024-05-25
United States64036491992-09-212012-09-21
Canada25856912009-05-192026-03-14
Canada21449672003-11-112013-09-09
Properties
Statesolid
Experimental Properties
PropertyValueSource
water solubilitySlightly solubleNot Available
logP3.2Not Available
Predicted Properties
PropertyValueSource
water solubility1.87e-02 g/lALOGPS
logP3.41ALOGPS
logP2.63ChemAxon
logS-4.3ALOGPS
pKa (strongest acidic)14.35ChemAxon
pKa (strongest basic)-0.23ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count4ChemAxon
hydrogen donor count4ChemAxon
polar surface area89.79ChemAxon
rotatable bond count12ChemAxon
refractivity122.83ChemAxon
polarizability48.99ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Jiang Xing Chen, “Process for the production of intermediates for making prostaglandin derivatives such as latanaprost, travaprost, and bimatoprost.” U.S. Patent US20090287003, issued November 19, 2009.

US20090287003
General Reference
  1. Chen MJ, Cheng CY, Chen YC, Chou CK, Hsu WM: Effects of bimatoprost 0.03% on ocular hemodynamics in normal tension glaucoma. J Ocul Pharmacol Ther. 2006 Jun;22(3):188-93. Pubmed
  2. Kruse P, Rieck P, Sherif Z, Liekfeld A: [Cystoid macular edema in a pseudophakic patient after several glaucoma procedures. Is local therapy with bimatoprost the reason?] Klin Monatsbl Augenheilkd. 2006 Jun;223(6):534-7. Pubmed
  3. Steinhauser SL: Decreased high-density lipoprotein serum levels associated with topical bimatoprost therapy. Optometry. 2006 Apr;77(4):177-9. Pubmed
  4. Woodward DF, Krauss AH, Chen J, Lai RK, Spada CS, Burk RM, Andrews SW, Shi L, Liang Y, Kedzie KM, Chen R, Gil DW, Kharlamb A, Archeampong A, Ling J, Madhu C, Ni J, Rix P, Usansky J, Usansky H, Weber A, Welty D, Yang W, Tang-Liu DD, Garst ME, Brar B, Wheeler LA, Kaplan LJ: The pharmacology of bimatoprost (Lumigan). Surv Ophthalmol. 2001 May;45 Suppl 4:S337-45. Pubmed
  5. Lim KS, Nau CB, O’Byrne MM, Hodge DO, Toris CB, McLaren JW, Johnson DH: Mechanism of action of bimatoprost, latanoprost, and travoprost in healthy subjects. A crossover study. Ophthalmology. 2008 May;115(5):790-795.e4. Pubmed
  6. Brubaker RF: Mechanism of action of bimatoprost (Lumigan). Surv Ophthalmol. 2001 May;45 Suppl 4:S347-51. Pubmed
  7. Christiansen GA, Nau CB, McLaren JW, Johnson DH: Mechanism of ocular hypotensive action of bimatoprost (Lumigan) in patients with ocular hypertension or glaucoma. Ophthalmology. 2004 Sep;111(9):1658-62. Pubmed
  8. Easthope SE, Perry CM: Topical bimatoprost: a review of its use in open-angle glaucoma and ocular hypertension. Drugs Aging. 2002;19(3):231-48. Pubmed
  9. Patil AJ, Vajaranant TS, Edward DP: Bimatoprost – a review. Expert Opin Pharmacother. 2009 Nov;10(16):2759-68. Pubmed
External Links
ResourceLink
PubChem Compound5311027
PubChem Substance46505334
ChemSpider4470565
ChEBI51230
ChEMBLCHEMBL1200963
Therapeutic Targets DatabaseDAP001217
PharmGKBPA164748867
IUPHAR1958
Guide to Pharmacology1958
HET15M
Drug Product Database2245860
RxListhttp://www.rxlist.com/cgi/generic2/bimatoprost.htm
Drugs.comhttp://www.drugs.com/cdi/bimatoprost-drops.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/lum1578.shtml
WikipediaBimatoprost
ATC CodesS01EE03
AHFS Codes
  • 52:92.00
PDB EntriesNot Available
FDA labelshow(24.4 KB)
MSDSshow(19.2 KB)
Interactions
Drug Interactions
Drug
LatanoprostThe concomitant use of bimatoprost and latanoprost may result in increased intraocular pressure. Consider avoiding this combination of therapy. Monitor for paradoxical increases in intraocular pressure during concomitant use.
Food InteractionsNot Available

Targets

1. Prostaglandin F2-alpha receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Prostaglandin F2-alpha receptor P43088 Details

References:

  1. Sharif NA, Williams GW, Kelly CR: Bimatoprost and its free acid are prostaglandin FP receptor agonists. Eur J Pharmacol. 2001 Dec 7;432(2-3):211-3. Pubmed
  2. Sharif NA, Kelly CR, Crider JY: Agonist activity of bimatoprost, travoprost, latanoprost, unoprostone isopropyl ester and other prostaglandin analogs at the cloned human ciliary body FP prostaglandin receptor. J Ocul Pharmacol Ther. 2002 Aug;18(4):313-24. Pubmed
  3. Sharif NA, Kelly CR, Crider JY, Williams GW, Xu SX: Ocular hypotensive FP prostaglandin (PG) analogs: PG receptor subtype binding affinities and selectivities, and agonist potencies at FP and other PG receptors in cultured cells. J Ocul Pharmacol Ther. 2003 Dec;19(6):501-15. Pubmed
  4. Lim KS, Nau CB, O’Byrne MM, Hodge DO, Toris CB, McLaren JW, Johnson DH: Mechanism of action of bimatoprost, latanoprost, and travoprost in healthy subjects. A crossover study. Ophthalmology. 2008 May;115(5):790-795.e4. Pubmed
  5. Mintz EE: Group supervision: an experiential approach. Int J Group Psychother. 1978 Oct;28(4):467-9. Pubmed
  6. Neacsu AM: [Receptors involved in the mechanism of action of topical prostaglandines] Oftalmologia. 2009;53(2):3-7. Pubmed
  7. Wan Z, Woodward DF, Cornell CL, Fliri HG, Martos JL, Pettit SN, Wang JW, Kharlamb AB, Wheeler LA, Garst ME, Landsverk KJ, Struble CS, Stamer WD: Bimatoprost, prostamide activity, and conventional drainage. Invest Ophthalmol Vis Sci. 2007 Sep;48(9):4107-15. Pubmed
  8. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Prostaglandin E2 receptor EP1 subtype

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Prostaglandin E2 receptor EP1 subtype P34995 Details

References:

  1. Sharif NA, Kelly CR, Crider JY, Williams GW, Xu SX: Ocular hypotensive FP prostaglandin (PG) analogs: PG receptor subtype binding affinities and selectivities, and agonist potencies at FP and other PG receptors in cultured cells. J Ocul Pharmacol Ther. 2003 Dec;19(6):501-15. Pubmed
  2. Ota T, Aihara M, Saeki T, Narumiya S, Araie M: The effects of prostaglandin analogues on prostanoid EP1, EP2, and EP3 receptor-deficient mice. Invest Ophthalmol Vis Sci. 2006 Aug;47(8):3395-9. Pubmed

3. Prostaglandin E2 receptor EP3 subtype

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Prostaglandin E2 receptor EP3 subtype P43115 Details

References:

  1. Sharif NA, Kelly CR, Crider JY, Williams GW, Xu SX: Ocular hypotensive FP prostaglandin (PG) analogs: PG receptor subtype binding affinities and selectivities, and agonist potencies at FP and other PG receptors in cultured cells. J Ocul Pharmacol Ther. 2003 Dec;19(6):501-15. Pubmed
  2. Gabelt BT, Hennes EA, Bendel MA, Constant CE, Okka M, Kaufman PL: Prostaglandin subtype-selective and non-selective IOP-lowering comparison in monkeys. J Ocul Pharmacol Ther. 2009 Feb;25(1):1-8. Pubmed
  3. Ota T, Aihara M, Saeki T, Narumiya S, Araie M: The effects of prostaglandin analogues on prostanoid EP1, EP2, and EP3 receptor-deficient mice. Invest Ophthalmol Vis Sci. 2006 Aug;47(8):3395-9. Pubmed

4. Aldo-keto reductase family 1 member C3

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Aldo-keto reductase family 1 member C3 P42330 Details

References:

  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12