Bimatoprost

Bimatoprost

Systematic (IUPAC) name
7-[3,5-dihydroxy-2- (3-hydroxy-5-phenyl-pent-1-enyl)- cyclopentyl]-N-ethyl-hept-5-enamide
Clinical data
Trade names	Lumigan
AHFS/Drugs.com	monograph
MedlinePlus	a602030
Licence data	US Daily Med:link
Pregnancy cat.	C (US)
Legal status	℞-only (US)
Routes	Topical (eye drops)
Identifiers
CAS number	155206-00-1 Y
ATC code	S01EE03
PubChem	CID 5311027
IUPHAR ligand	1958
DrugBank	DB00905
ChemSpider	4470565 Y
UNII	QXS94885MZ Y
ChEBI	CHEBI:51230 Y
ChEMBL	CHEMBL1200963 N
Chemical data
Formula	C25H37NO4
Mol. mass	415.566 g/mol
SMILES O=C(NCC)CCC/C=C\C[C@H]2[C@@H](O)C[C@@H](O)[C@@H]2/C=C/[C@@H](O)CCc1ccccc1
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 Y Key:AQOKCDNYWBIDND-FTOWTWDKSA-N Y
N (what is this?)  (verify)

Bimatoprost (marketed in the U.S., Canada and Europe by Allergan, under the trade name Lumigan) is a prostaglandin analog/prodrug used topically (as eye drops) to control the progression of glaucoma and in the management of ocular hypertension. It reduces intraocular pressure (IOP) by increasing the outflow of aqueous fluid from the eyes.^[1] In December 2008, the indication to lengthen eyelashes was approved by the U.S. Food and Drug Administration (FDA); the cosmetic formulation of bimatoprost is sold as Latisse /ləˈtiːs/.^[2] In 2008-2011, at least three case series suggested that bimatoprost has the ability to reduce adipose (fat) tissue.^[3][4][5]

Cosmetic use

In patients using ophthalmic prostaglandins such as travoprost and latanoprost, it has been anecdotally noted that there had been an increase in diameter, density and length of eyelashes. Allergan has initiated clinical trials investigating the usage of Lumigan as a cosmetic drug.^[6] On December 5, 2008, the FDA Dermatologic and Ophthalmic Drugs Advisory Committee voted to approve bimatoprost for the cosmetic use of darkening and lengthening eyelashes.^{[citation needed]} The medical term for this is treatment of hypotrichosis, however, the FDA approval is for purely cosmetic purposes.^[7]

For cosmetic purposes, it is administered once daily by applying the solution to the skin at the base of the eyelash using an applicator device "Application Guide", where it has its effect upon the hair follicle.

Bimatoprost activates prostamide alpha F2 receptors found in the hair follicle to stimulate its growth rate. Research led by Professor Randall and the University of Bradford found that it may also offer a treatment for scalp hair regrowth in trials conducted on samples taken from men undergoing hair transplants.^[8]

According to Allergan's package labeling, users of its Latisse cosmetic product didn't develop darker irises in clinical studies; however, "patients should be advised about the potential for increased brown iris pigmentation which is likely to be permanent."^[9]

Several cosmetics companies have released products based on prostaglandin analogs, as non-drug cosmetics.

• Age Intervention Eyelash by Jan Marini Skin Research
• RevitaLash by Athena Cosmetics Corp.

These companies have been sued by Allergan for patent infringement.^[6] The FDA has seized Age Intervention Eyelash as an "unapproved and misbranded drug" because Jan Marini Skin Research promoted it as something that increases eyelash growth^[10] and because it is "adulterated" with bimatoprost.^[11]

Fat-reducing properties

Reductions in orbital fat (i.e., fat around the eye) have been observed in patients using bimatoprost as glaucoma therapy.^[12] Of particular interest, the loss of orbital fat was unilateral in patients who used bimatoprost on only one eye.^[13] The effect appears reversible upon cessation of bimatoprost use.^{[citation needed]} The effect is likely to explain deepening of the lid sulcus described in a series of three patients on bimatoprost.^[14] The mechanism for the apparent fat reduction remains unclear. However, bimatoprost is chemically analogous to prostaglandin F_2α (PGF_2α), a compound which is known to reduce fat by inhibition of adipocyte differentiation and survival.^[15]

Formulations

Lumigan is a 0.03% solution of bimatoprost, and contains benzalkonium chloride as a preservative. Contact lenses should therefore be removed before use, and replaced no less than 15 minutes later;^[1] other eye drops or ointments should be given no less than five minutes before or after bimatoprost.^[1]

Efficacy

Studies have shown once-daily bimatoprost 0.03% ophthalmic solution to be more effective than timolol twice daily in reduction of intraocular pressure (IOP) and as effective as or more effective than the prostaglandin analogues latanoprost and travoprost in reducing IOP.^[16]

Side effects

Possible side effects of this medication are:^{[citation needed]}

• May cause blurred vision.
• May cause eyelid redness.
• May permanently darken eyelashes.
• May cause eye discomfort.
• May eventually cause permanent darkening of the iris to brown.
• May cause a temporary burning sensation during use.
• May cause thickening of the eyelashes.
• It may cause unexpected growth of hair if applied inappropriately, on the cheek, for example.
• It may cause infection if the one-time applicators which come with the genuine product are reused.
• Lashes may grow so long that they become ingrown and scratch the cornea.
• May cause darkening of the eyelid or of the area beneath the eye.^[17]

On November 19, 2007, the FDA issued a warning during the seizure of a bimatoprost-containing cosmetic.^[18] The warning stated that "the extra dose of bimatoprost may decrease the prescription drug's effectiveness. Damage to the optic nerve may lead to decreased vision and possibly blindness."

References

Citations

• Chen M, Cheng C, Chen Y, Chou C, Hsu W (2006). "Effects of bimatoprost 0.03% on ocular hemodynamics in normal tension glaucoma.". J Ocul Pharmacol Ther 22 (3): 188–93. doi:10.1089/jop.2006.22.188. PMID 16808680. 
• Kruse P, Rieck P, Sherif Z, Liekfeld A (2006). "Cystoid macular edema in a pseudophakic patient after several glaucoma procedures. Is local therapy with bimatoprost the reason?". Klinische Monatsblätter für Augenheilkunde 223 (6): 534–7. doi:10.1055/s-2005-858992. PMID 16804825. 
• Steinhäuser S (2006). "Decreased high-density lipoprotein serum levels associated with topical bimatoprost therapy.". Optometry 77 (4): 177–9. doi:10.1016/j.optm.2006.02.001. PMID 16567279. 
• Park J, Cho HK, Moon JI (2011). "Changes to upper eyelid orbital fat from use of topical bimatoprost, travoprost, and latanoprost.". Japanese Ophthalmological Society 55 (1): 22–27. doi:10.1007/s10384-010-0904-z. PMID 21331688. 
• Jayaprakasam A, Ghazi-Nouri S. (2010). "Periorbital fat atrophy - an unfamiliar side effect of prostaglandin analogues.". Orbit 29 (6): 357–359. doi:10.3109/01676830.2010.527028. PMID 21158579. 
• Filippopoulos T, Paula JS, Torun N, Hatton MP, Pasquale LR, Grosskreutz CL. (2008). "Periorbital changes associated with topical bimatoprost.". Ophthalmology Plastic and Reconstructive Surgery 24 (4): 302–307. doi:10.1097/IOP.0b013e31817d81df. PMID 18645437. 

External links

• Medical News Today: FDA Seizes $2 Million Of Cosmetic Eye Product Which Contains Drug Ingredient And Makes Unapproved Drug Claims. Christian Nordqvist. 18 November 2007
• Wired Science: FDA Seizes Cosmetic That Can Blind. Brandon Keim. November 19, 2007

• Eye Drops: [The generic name of the Latisse eye drop is Bimatoprost Ophthalmic Solution 0.03%]. Crazzy Paul. Aug 01, 2013