DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more

Acular (Ketorolac Tromethamine Ophthalmic) - Description and Clinical Pharmacology

 
 



ACULAR®
(ketorolac tromethamine ophthalmic solution) 0.5%
sterile

DESCRIPTION

ACULAR® (ketorolac tromethamine ophthalmic solution) is a member of the pyrrolo-pyrrole group of nonsteroidal anti-inflammatory drugs (NSAIDs) for ophthalmic use. Its chemical name is (±)-5-benzoyl-2, 3-dihydro-1H pyrrolizine-1-carboxylic acid, compound with 2-amino-2-(hydroxymethyl)-1,3-propanediol (1:1) and it has the following structure:

ACULAR® ophthalmic solution is supplied as a sterile isotonic aqueous 0.5% solution, with a pH of 7.4. ACULAR® ophthalmic solution is a racemic mixture of R-(+) and S-(-)- ketorolac tromethamine. Ketorolac tromethamine may exist in three crystal forms. All forms are equally soluble in water. The pKa of ketorolac is 3.5. This white to off-white crystalline substance discolors on prolonged exposure to light. The molecular weight of ketorolac tromethamine is 376. 41. The osmolality of ACULAR® ophthalmic solution is 290 mOsml/kg.

Each mL of ACULAR® ophthalmic solution contains: Active: ketorolac tromethamine 0.5%. Preservative: benzalkonium chloride 0.01%. Inactives: edetate disodium 0.1%; octoxynol 40; purified water; sodium chloride; and hydrochloric acid and/or sodium hydroxide to adjust the pH.

CLINICAL PHARMACOLOGY

Ketorolac tromethamine is a nonsteroidal anti-inflammatory drug which, when administered systemically, has demonstrated analgesic, anti-inflammatory, and anti-pyretic activity. The mechanism of its action is thought to be due to its ability to inhibit prostaglandin biosynthesis. Ketorolac tromethamine given systemically does not cause pupil constriction.

Prostaglandins have been shown in many animal models to be mediators of certain kinds of intraocular inflammation. In studies performed in animal eyes, prostaglandins have been shown to produce disruption of the blood-aqueous humor barrier, vasodilation, increased vascular permeability, leukocytosis, and increased intraocular pressure. Prostaglandins also appear to play a role in the miotic response produced during ocular surgery by constricting the iris sphincter independently of cholinergic mechanisms.

Two drops (0.1 mL) of 0.5% ACULAR® ophthalmic solution instilled into the eyes of patients 12 hours and 1 hour prior to cataract extraction achieved measurable levels in 8 of 9 patients' eyes (mean ketorolac concentration 95 ng/mL aqueous humor, range 40 to 170 ng/mL). Ocular administration of ketorolac tromethamine reduces prostaglandin E2 (PGE2) levels in aqueous humor. The mean concentration of PGE2 was 80 pg/mL in the aqueous humor of eyes receiving vehicle and 28 pg/mL in the eyes receiving ACULAR® 0.5% ophthalmic solution.

One drop (0.05 mL) of 0.5% ACULAR® ophthalmic solution was instilled into one eye and one drop of vehicle into the other eye TID in 26 normal subjects. Only 5 of 26 subjects had a detectable amount of ketorolac in their plasma (range 10.7 to 22.5 ng/mL) at Day 10 during topical ocular treatment. When ketorolac tromethamine 10 mg is administered systemically every 6 hours, peak plasma levels at steady state are around 960 ng/mL.

Two controlled clinical studies showed that ACULAR® ophthalmic solution was significantly more effective than its vehicle in relieving ocular itching caused by seasonal allergic conjunctivitis.

Two controlled clinical studies showed that patients treated for two weeks with ACULAR® ophthalmic solution were less likely to have measurable signs of inflammation (cell and flare) than patients treated with its vehicle.

Results from clinical studies indicate that ketorolac tromethamine has no significant effect upon intraocular pressure; however, changes in intraocular pressure may occur following cataract surgery.

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2012