Singapore Drugs Database

Indication

For the short-term (~5 days) management of moderately severe acute pain that requires analgesia at the opioid level, usually in a postoperative setting.

Mechanism of Action

Ketorolac is a nonsteroidal anti-inflammatory drug (NSAID) chemically related to indomethacin and tolmetin. Ketorolac tromethamine is a racemic mixture of [-]S- and [+]R-enantiomeric forms, with the S-form having analgesic activity. Its antiinflammatory effects are believed to be due to inhibition of both cylooxygenase-1 (COX-1) and cylooxygenase-2 (COX-2) which leads to the inhibition of prostaglandin synthesis leading to decreased formation of precursors of prostaglandins and thromboxanes from arachidonic acid. The resultant reduction in prostaglandin synthesis and activity may be at least partially responsible for many of the adverse, as well as the therapeutic, effects of these medications. Analgesia is probably produced via a peripheral action in which blockade of pain impulse generation results from decreased prostaglandin activity. However, inhibition of the synthesis or actions of other substances that sensitize pain receptors to mechanical or chemical stimulation may also contribute to the analgesic effect. In terms of the ophthalmic applications of ketorolac - ocular administration of ketorolac reduces prostaglandin E2 levels in aqueous humor, secondary to inhibition of prostaglandin biosynthesis.

Pharmacokinetics

Absorption

Rapidly and completely absorbed after oral administration

Distribution

* 0.26 ± 0.08 L/kg [children 4 to 8 years old]

Metabolism

Primarily hepatic. Less than 50% of a dose is metabolized. The major metabolites are a glucuronide conjugate, which may also be formed in the kidney, and p-hydroxy ketorolac. Neither metabolite has significant analgesic activity.

Elimination

Clearance

* 0.042 +/- 0.01 L/hr/kg [Pediatric Patients] * 0.02 L/h/kg [Normal Subjects IM] * 0.03 L/h/kg [Normal Subjects oral] * 0.02 L/h/kg [Healthy Elderly Subjects IM] * 0.02 L/h/kg [Healthy Elderly Subjects oral] * 0.03 L/h/kg [Patients with Hepatic Dysfunction IM] * 0.03 L/h/kg [Patients with Hepatic Dysfunction oral] * 0.02 L/h/kg [Patients with Renal Impairment IM] * 0.02 L/h/kg [Patients with Renal Impairment oral] * 0.02 L/h/kg [Renal Dialysis Patients IM]

Toxicity

LD₅₀ = 189 mg/kg (rat, oral).

Active Ingredient/Synonyms

(+-)-5-Benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid | (+-)-Ketorolac | Ketorolac | Kétorolac | Ketorolaco | Ketorolacum | rac-Ketorolac | Ketorolac |