title: Ketorolac tromethamine pharmacokinetics and metabolism after intravenous, intramuscular, and oral administration in humans and animals.
abstract: 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 (greater than 99%). The mean plasma elimination half-life is 5-6 hours, and ketorolac is not extensively distributed outside the vascular compartment (Vd beta 15 L). Virtually all of the drug-related material circulating in plasma is in the form of ketorolac (greater than 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.
authors.affiliation: Syntex Research, Palo Alto, California 94304.
authors.forename: E J
authors.initials: EJ
authors.lastname: Mroszczak
authors.forename: D
authors.initials: D
authors.lastname: Jung
authors.forename: J
authors.initials: J
authors.lastname: Yee
authors.forename: L
authors.initials: L
authors.lastname: Bynum
authors.forename: H
authors.initials: H
authors.lastname: Sevelius
authors.forename: I
authors.initials: I
authors.lastname: Massey
mesh_terms: D000284:Administration, Oral; D000536:Aluminum Hydroxide / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004338:Drug Combinations; D005260:Female; D005502:Food; D006207:Half-Life; D006801:Humans; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D020910:Ketorolac; D020911:Ketorolac Tromethamine; D008276:Magnesium Hydroxide / Q000494:pharmacology; D008297:Male; D008657:Metabolic Clearance Rate; D014018:Tissue Distribution; D014046:Tolmetin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D014325:Tromethamine / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004338:Drug Combinations; D014325:Tromethamine; C013591:aluminum hydroxide, magnesium hydroxide, drug combination; D020911:Ketorolac Tromethamine; D000536:Aluminum Hydroxide; D014046:Tolmetin; D008276:Magnesium Hydroxide; D020910:Ketorolac