Bromfenac sodium

Originator

Duract,Wyeth-Ayerst

Uses

Bromfenac (Xibrom, ISTA Pharmaceuticals, Irvine, USA; Bronuck, Senju Pharmaceutical, Osaka, Japan) is indicated for the treatment of postoperative inflammation and the reduction of ocular pain in patients after undergoing cataract extraction. For this task, one drop of Xibrom may be applied to the affected eye twice daily beginning 24 hours after cataract surgery and continuing for the first 2 weeks of the postoperative period. The clinical safety and efficacy of bromfenac have been extensively studied in diverse comparative investigations, including the treatment of external or anterior ocular inflammatory diseases, allergic conjunctivitis, scleritis, and postoperative inflammation.The results of two phase III multicenter, randomized double-masked placebo-controlled clinical trials showed that bromfenac ophthalmic solution 0.09% was effective in the rapid resolution of ocular pain after cataract surgery, and there was a statistically significant difference between the bromfenac and placebo groups demonstrated in these phase III clinical trials.

Uses

Analgesic.

Definition

ChEBI: Amfenac in which the the hydrogen at the 4 position of the benzoyl group is substituted by bromine. It is used for the management of ocular pain and treatment of postoperative inflammation in patients who have undergone cataract extraction. It was withdraw from the US market in 1998, following concerns over off-label abuse and hepatic failure.

Manufacturing Process

Reaction of (2-aminophenyl)-(4-bromophenyl)-methanone with methylsulfanylacetic acid ethyl ester and tert-butyl hypochlorite gives a corresponding sulfonium salt. This salt was transformed to initially to the betaine. Electrocyclic rearrangement of that transient intermediate leads, after rearomatization, to the homoanthranilic acid. Internal ester-amine interchange leads then to 4-bromophenyl-(3-(methylthio)indolin-7-yl)methanone. The thiomethyl group is then removed with Raney nickel to give 4-bromophenyl- (indolin-7-yl)methanone. Saponification of this intermediate affords the (2- amino-3-(4-bromobenzoyl)-phenyl)-acetic acid (Bromfenac).
In practice it is usually used as sodium salt.

brand name

Xibrom (Ista).

Therapeutic Function

Analgesicá Antiinflammatory

Pharmacology

The drug is rapidly absorbed and excreted. The drug’s long duration of anti-inflammatory action despite its short half-life deserves further investigation.

Clinical Use

Bromfenac, used as the sodium salt, is a non-steroidal anti-inflammatory drug acting via inhibition of COX-1 and COX-2. It was launched in Japan in 2000 by Senju for topical treatment of ocular inflammation and has been approved in the United States in 2006 for the treatment of pain following cataract surgery. It was used for the short-term treatment of acute pain, but it was withdrawn for this indication in June 1998 because of several postmarketing reports of severe hepatic failure

Synthesis

The cyclization of 2-amino-4’- bromobenzophenone with ethyl 2-(methylthio) acetate with tert-butyl hypochlorite as catalyst in dichloromethane at 70 ?C gives 7- (4-bromobenzoyl)-3-(methylthio)-2,3-dihydro- 1H-indol-2-one, which is desulfurized by treatment with Raney nickel in THF yielding 7-(4- bromobenzoyl)-2,3-dihydro-1H-indol-2-one. Finally, this compound is hydrolyzed with refluxing 3 M aqueous NaOH and acidified with concentrated HCl .

Veterinary Drugs and Treatments

Bromfenac is a nonsteroidal anti-inflammatory drug (NSAID) by virtue of its ability to block prostaglandin synthesis by inhibiting cyclooxygenase 1 and 2. Bromfenac is indicated for treatment of postoperative inflammation in patients who have undergone cataract extraction.