Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2024 Publisher: Atnahs Pharma UK Limited, Sovereign House, Miles Gray Road, Basildon, Essex, SS14 3FR, United Kingdom
Pharmacotherapeutic group: Anti-inflammatory and antirheumatic products, non-steroids
ATC code: M01AB15
Toradol is a potent analgesic agent of the non-steroidal, anti-inflammatory class (NSAID). It is not an opioid and has no known effects on opioid receptors. Its mode of action is to inhibit the cyclooxygenase enzyme system and hence prostaglandin synthesis, and it demonstrates a minimal anti-inflammatory effect at its analgesic dose.
IM: Following intramuscular administration, ketorolac trometamol was rapidly and completely absorbed, a mean peak plasma concentration of 2.2 mcg/ml occurring an average of 50 minutes after a single 30 mg dose. The influences of age, kidney and liver function on terminal plasma half-life and mean total clearance are outlined in the table below (estimated from a single 30 mg IM dose of ketorolac).
| Type of subjects | Total clearance (l/hr/kg) mean (range) | Terminal half-life (hrs) mean (range) |
| Normal subjects (n 4) | 0.023 (0.010 - 0.046) | 5.3 (3.5 - 9.2) |
| Patients with hepatic dysfunction (n=7) | 0.029 (0.013 - 0.066) | 5.4 (2.2 - 6.9) |
| Patients with renal impairment (n=25) (serum creatinine 160 - 430 micromol/l) | 0.016 (0.005 - 0.043) | 10.3 (5.9 - 19.2) |
| Renal dialysis patients (n=9) | 0.016 (0.003 - 0.036) | 13.6 (8.0 - 39.1) |
| Healthy elderly subjects (n=13) (mean age 72) | 0.019 (0.013 - 0.034) | 7.0 (4.7 - 8.6) |
IV: Intravenous administration of a single 10 mg dose of ketorolac trometamol resulted in a mean peak plasma concentration of 2.4 mcg/ml occurring an average of 5.4 minutes after dosing, with a terminal plasma elimination half-life of 5.1 hours, an average volume of distribution of 0.15 l/kg, and a total plasma clearance of 0.35 ml/min/kg.
The pharmacokinetics of ketorolac in man following single or multiple doses are linear. Steady-state plasma levels are achieved after dosing every 6 hours for one day. No changes in clearance occurred with chronic dosing. The primary route of excretion of ketorolac and its metabolites is renal: 91.4% (mean) of a given dose being found in the urine and 6.1% (mean) in the faeces.
More than 99% of the ketorolac in plasma is protein-bound over a wide concentration range.
An 18-month study in mice with oral doses of ketorolac trometamol at 2 mg/kg/day (0.9 times human systemic exposure at the recommended IM or IV dose of 30 mg qid, based on area-under-the-plasma-concentration curve [AUC]), and a 24-month study in rats at 5 mg/kg/day (0.5 times the human AUC), showed no evidence of tumorigenicity.
Ketorolac trometamol was not mutagenic in the Ames test, unscheduled DNA synthesis and repair, and in forward mutation assays. Ketorolac trometamol did not cause chromosome breakage in the in vivo mouse micronucleus assay. At 1590 mcg/ml and at higher concentrations, ketorolac trometamol increased the incidence of chromosomal aberrations in Chinese hamster ovarian cells.
Impairment of fertility did not occur in male or female rats at oral doses of 9 mg/kg (0.9 times the human AUC) and 16 mg/kg (1.6 times the human AUC) of ketorolac trometamol, respectively.
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