KETOROLAC TROMETHAMINE PHARMACOKINETICS AND METABOLISM AFTER INTRAVENOUS, INTRAMUSCULAR, AND ORAL-ADMINISTRATION IN HUMANS AND ANIMALS

In humans, ketorolac is completely bioavailable and its kinetics are linear. It is absorbed rapidly (half-life for absorption 3.8 min) after oral (fasting) and intramuscular administration; food delays but does not reduce its absorption. The drug is highly protein bound in humans (> 99%). The mean plasma elimination half-life is 5-6 hours, and ketorolac is not extensively distributed outside the vascular compartment (V(d-beta) 15 L). Virtually all of the drug-related material circulating in plasma is in the form of ketorolac (> 96%), with the only metabolite the pharmacologically inactive p-hydroxyketorolac (PHK). Humans excrete about 90% of the administered dose in urine. About 60% of drug-related material recovered from urine is ketorolac, about 12% is PHK, and 28% represents polar, glucuronide conjugates of ketorolac. The animal models in which ketorolac's metabolism and kinetics are most similar to those in humans are the mouse and monkey, respectively.