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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 (Vd815 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.