| 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. |
| Pharmacodynamics |
Ketorolac, an antiinflammatory agent with analgesic and
antipyretic properties, is used to treat osteoarthritis and control
acute pain. It is a peripherally acting analgesic. The biological
activity of ketorolac tromethamine is associated with the S-form.
Ketorolac tromethamine possesses no sedative or anxiolytic properties. |
| 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. |
| Absorption |
Rapidly and completely absorbed after oral administration |
| Volume of distribution |
- 0.26 ± 0.08 L/kg [children 4 to 8 years old]
|
| Protein binding |
99% |
| 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. |
| Route of elimination |
The principal route of elimination of ketorolac and its
metabolites is renal. Approximately 6% of a dose is excreted in the
feces. |
| Half life |
2.5 hours for the S-enantiomer compared with 5 hours for the R-enantiomer |
| 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). |
