bromfenac

ブロムフェナク

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/08/06 14:46:45」(JST)

wiki en

[Wiki en表示]

Bromfenac

Systematic (IUPAC) name
2-[2-amino-3-(4-bromobenzoyl)phenyl]acetic acid
Clinical data
Trade names	Bromday
AHFS/Drugs.com	monograph
MedlinePlus	a611018
Pregnancy cat.	C
Legal status	℞-only (US)
Routes	Oral (discontinued) ophthalmic
Identifiers
CAS number	91714-94-2 Y
ATC code	S01BC11
PubChem	CID 60726
DrugBank	DB00963
ChemSpider	54730 Y
UNII	864P0921DW Y
KEGG	D07541 Y
ChEBI	CHEBI:240107 Y
ChEMBL	CHEMBL1077 Y
Chemical data
Formula	C15H12BrNO3
Mol. mass	334.16g/mol
SMILES O=C(c1ccc(Br)cc1)c2cccc(c2N)CC(=O)O
InChI InChI=1S/C15H12BrNO3/c16-11-6-4-9(5-7-11)15(20)12-3-1-2-10(14(12)17)8-13(18)19/h1-7H,8,17H2,(H,18,19) Y Key:ZBPLOVFIXSTCRZ-UHFFFAOYSA-N Y
Y (what is this?)  (verify)

Bromfenac is a non-steroidal anti-inflammatory drug (NSAID) marketed in the US as an ophthalmic solution (current brand name Bromday, prior formulation brand name Xibrom, which has since been discontinued.) by ISTA Pharmaceuticals for short-term, local use. Bromday is the once-daily formulation of bromfenac, while Xibrom, which has since been discontinued, was the twice-daily formulation. Bromfenac is indicated for the treatment of ocular inflammation and pain after cataract surgery, though it may be prescribed in an off-label manner by the physician.

For ophthalmic use, bromfenac has been prescribed more than 20,000,000 times across the world. As an eye drop, it has been available since 2000, starting in Japan where it was sold as Bronuck. It was first FDA approved for use in the United States in 2005 and it was marketed as Xibrom, twice-daily. October 2010 was the FDA approval of the new once-daily formulation of bromfenac called Bromday. The bromfenac molecule will be marketed in Europe and other worldwide markets with agreements from Bausch & Lomb, Croma Pharma, and other companies.

Bromfenac was formerly marketed in the United States by Wyeth-Ayerst in an oral formulation called Duract for short-term relief of pain (less than 10 days at a time). It was brought to market in July, 1997, and was withdrawn June 22, 1998 following numerous reports of hepatotoxicity in patients who had taken the medication for longer than the recommended 10-day period. The dose was one 25 mg capsule every 6 to 8 hours, or two capsules if taken with a high-fat meal, up to a maximum of 150 mg per day.

Clinical use

The FDA approval for Bromday is for use one day before and two weeks following cataract surgery for the treatment of ocular inflammation and pain.

Pharmacology and clinical studies

The high degree of penetration and potency of bromfenac can be attributed to the halogenation of the molecule: by adding a bromine moiety the NSAID becomes highly lipophilic which allows for rapid, sustained drug levels in the ocular tissues.

The Bromfenac Comparative trial was done to determine the optimal concentration for a once daily formulation. The standard 0.09% concentration performed as well as a double strength 0.18% concentration indicating that the COX enzyme receptors were already saturated and blocked by the bromfenac molecule.

In the Bromday FDA Pivotal Trial patients were evaluated with two end-points: a primary efficacy endpoint of the summed ocular inflammation score (SOIS) at post-operative day 15 and a secondary efficacy endpoint of patients reporting a pain score of “none” on post-operative day 1. Note that both arms of this study, the Bromday arm and the placebo arm, were not given any sort of corticosteroid to control inflammation. All anti-inflammatory activity for these post-op cataract patients was from the Bromday NSAID alone.

For post-operative inflammation at day 15, the patients receiving bromfenac had an SOIS level of just 1.1 compared to 2.8 for the patients in the placebo arm. This was statistically significant with a P value of <0.0001 for day 3, day 8, day 15, and day 22. When patients were asked about their pain level the day after surgery, after having received a total of three drops of bromfenac (pre-op day, day of surgery, post-op day 1), 94.8% of patients reported “none”, compared to 70.5% for placebo.

Patients who had lack of efficacy were allowed to exit the trial as a safety and comfort measure. For patients receiving bromfenac, only 2.9% of bromfenac patients elected to do so. This is more than 10 times better than the placebo group where nearly 33% of patients discontinued their participation in the study. These results show that Bromday given just once per day, as a sole anti-inflammatory agent was clinically effective at reducing post-operative inflammation and pain.

Bromfenac is the first of a new generation of post-operative medications with once daily dosing.

Chemistry

Bromfenac can be synthesized by the route outlined below.

References

External links

• Bromday homepage

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 成人における白内障 cataract in adults
• 2. 成人女性における原発性月経困難症の治療 treatment of primary dysmenorrhea in adult women
• 3. 春季カタル vernal keratoconjunctivitis

English Journal

• Bromfenac ophthalmic solution 0.07% dosed once daily for cataract surgery: results of 2 randomized controlled trials.

• Walters TR1, Goldberg DF2, Peace JH3, Gow JA4; Bromfenac Ophthalmic Solution 0.07% Once Daily Study Group.Author information 1Texan Eye, Austin, Texas.2Wolstan Eye Associates, Torrance, California.3United Medical Research Institute, Inglewood, California.4Bausch and Lomb, Inc, Irvine, California.AbstractPURPOSE: To evaluate the efficacy and ocular safety of bromfenac ophthalmic solution 0.07% (Prolensa) dosed once daily for the treatment of ocular inflammation and pain in subjects who underwent cataract surgery with posterior chamber intraocular lens implantation.
• Ophthalmology.Ophthalmology.2014 Jan;121(1):25-33. doi: 10.1016/j.ophtha.2013.07.006. Epub 2013 Sep 8.
• PURPOSE: To evaluate the efficacy and ocular safety of bromfenac ophthalmic solution 0.07% (Prolensa) dosed once daily for the treatment of ocular inflammation and pain in subjects who underwent cataract surgery with posterior chamber intraocular lens implantation.DESIGN: Two phase 3, randomized, do
• PMID 24021896

• Trabecular Meshwork Bradykinin Receptors: mRNA Levels, Immunohistochemical Visualization, Signaling Processes Pharmacology, and Linkage to IOP Reduction.

• Sharif NA, Katoli P, Kelly CR, Li L, Xu S, Wang Y, Klekar L, Earnest D, Yacoub S, Hamilton G, Jacobson N, Shepard AR, Ellis D.Author information 1 Pharmaceutical Research, Alcon Research, Ltd. (A Novartis Company) , Fort Worth, Texas.AbstractAbstract Purpose: To localize mRNA and protein of bradykinin (BK) receptors, BK precursor polypeptide (kininogen) mRNA, and to study functional biochemical pharmacology of the signal transduction processes mediated by B2-receptors in isolated human trabecular meshwork (h-TM) cells. Intraocular pressure (IOP) lowering effects of 2 kinins were also investigated. Methods: Previously documented procedures were utilized throughout these studies. Results: Kinninogen mRNA was most abundant in TM, ciliary body (CB), and optic nerve head and appeared elevated in glaucomatous h-TM tissue. High levels of B2-receptor mRNA were found in the sclera, iris, TM, and CB. B2-receptor subtype protein was localized in cells of the monkey and h-TM, and the treatment of isolated h-TM cells with transforming growth factor-β2 (5 ng/mL) caused significant (P<0.04) downregulation of B2-receptor mRNA. In isolated primary h-TM cells, BK (EC50=0.8±0.2 nM; n=19) and Met-Lys-BK (EC50=6.5±1.5 nM) mobilized intracellular Ca2+ and induced the release of prostaglandins (PGs) that was blocked by 2 B2-receptor antagonists [HOE-140; (S)-WIN-64338]. The cyclooxygenase inhibitor, bromfenac, abolished BK-induced PGs production. BK concentration dependently increased cell impedance, and it significantly (P<0.05) decreased h-TM cell volume in vitro. Intravitreal (ivt) administration of BK (50 μg), but not a B1-agonist (Sar-[D-Phe9]-Des-Arg9-BK; also at 50 μg), efficaciously lowered IOP (22.9% to 37% from baseline) of Dutch-Belted rabbits that naturally have high IOPs (27-28 mmHg). Conclusions: BK activates multiple signal transduction pathways in h-TM cells via B2-receptors that also mediate IOP reduction as observed in rabbits following ivt administration of BK. These ocular hypotensive effects of BK may be physiologically important and suggest a novel therapeutic potential of BK-related B2-agonists.
• Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics.J Ocul Pharmacol Ther.2013 Nov 16. [Epub ahead of print]
• Abstract Purpose: To localize mRNA and protein of bradykinin (BK) receptors, BK precursor polypeptide (kininogen) mRNA, and to study functional biochemical pharmacology of the signal transduction processes mediated by B2-receptors in isolated human trabecular meshwork (h-TM) cells. Intraocular press
• PMID 24236827

• Identification of PPARγ ligands with One-dimensional Drug Profile Matching.

• Kovács D, Simon Z, Hári P, Málnási-Csizmadia A, Hegedűs C, Drimba L, Németh J, Sári R, Szilvássy Z, Peitl B.Author information Department of Pharmacology and Pharmacotherapy, University of Debrecen, Nagyerdei Boulevard 98, Debrecen, Hungary.AbstractINTRODUCTION: Computational molecular database screening helps to decrease the time and resources needed for drug development. Reintroduction of generic drugs by second medical use patents also contributes to cheaper and faster drug development processes. We screened, in silico, the Food and Drug Administration-approved generic drug database by means of the One-dimensional Drug Profile Matching (oDPM) method in order to find potential peroxisome proliferator-activated receptor gamma (PPARγ) agonists. The PPARγ action of the selected generics was also investigated by in vitro and in vivo experiments.
• Drug design, development and therapy.Drug Des Devel Ther.2013 Sep 2;7:917-28. doi: 10.2147/DDDT.S47173.
• INTRODUCTION: Computational molecular database screening helps to decrease the time and resources needed for drug development. Reintroduction of generic drugs by second medical use patents also contributes to cheaper and faster drug development processes. We screened, in silico, the Food and Drug Ad
• PMID 24039401

Japanese Journal

• Cytotoxicity of Topical Medications Used for Infection and Inflammation Control after Cataract Surgery in Cultured Corneal Endothelial Cells

• AYAKI MASAHIKO,TAGUCHI YOKO,SODA MITSUTAKA,YAGUCHI SHIGEO,IWASAWA ATSUO,KOIDE RYOHEI
• Biocontrol science 15(3), 97-102, 2010-09-10
• … A range of commercially available antibiotic and anti-inflammatory ophthalmic solutions used postoperatively, namely levofloxacin, moxifloxacin, gatifloxacin, cefmenoxime, diclofenac, bromfenac, pranoprofen, betamethasone, and fluoromethorone, were assessed by using human corneal endothelial cells (HCECs). …
• NAID 10026730637

• 白内障と後発白内障の組織化学的解明

• 向井 公一郎
• 日本白内障学会誌 22, 5-16, 2010-06-15
• NAID 10026622040

Related Links

• Bromfenac - Wikipedia, the free encyclopedia

Bromfenac is a non-steroidal anti-inflammatory drug (NSAID) marketed in the US as an ophthalmic solution (current brand name Bromday, prior formulation brand name Xibrom, which has since been discontinued.) by ISTA Pharmaceuticals ...

• Xibrom (Bromfenac Ophthalmic Solution) Drug Information ... - RxList

Learn about the prescription medication Xibrom (Bromfenac Ophthalmic Solution ), drug uses, dosage, side effects, drug interactions, warnings, reviews and patient labeling.

Related Pictures

---

★リンクテーブル★

リンク元	「ブロムフェナク」
拡張検索	「bromfenac sodium」

「ブロムフェナク」

　　[★]

英

bromfenac

化

ブロムフェナクナトリウム水和物, bromfenac sodium hydrate、ブロムフェナクナトリウム, bromfenac sodium

商

ブロナック, Bronuck

関

非ステロイド性抗炎症薬

• 酸性非ステロイド性抗炎症薬

「bromfenac sodium」

　　[★] ブロムフェナク、ブロムフェナクナトリウム