DRUG DISPOSITION nino Pharmacokinel. 23 (6): 415-427. 1992 0312-5963/ 92/0012-0415/$06.50/0 © Adis International Limited. All rights reserved. CPK1240 Clinical Pharmacokinetics of Ketorolac Tromethamine Dian R. Bracks and Fakhreddin Jama/i Faculty of Pharmacy and Pharmaceutical Sciences. University of Alberta. Edmonton. Alberta. Canada Contents 415 416 417 417 419 420 421 423 423 424 424 425 425 425 426 Summary Summary I. Analytical Methods 2. Pharmacokinetic Properties 2.1 Absorption 2.2 Distribution 2.3 Elimination 3. Stereoselective Pharmacokinetics 4. Implications of Pharmacokinetic Properties for Therapeutic Use 4.1 Dosage and Therapeutic Range 4.2 Influence of Age on Ketorolac Pharmacokinetics 4.3 Effects of Renal and Hepatic Diseases 5. Pharmacokinetic Drug Interactions 5. 1 Effect of Other Drugs on the Pharmacokinetics of Ketorolac 5.2 Effect of Ketorolac on the Pharmacokinetics of Other Drugs 6. Conclusions Ketorolac is a new chiral nonsteroidal anti-inflammatory drug (NSAID) which is marketed for analgesia as the racemate. The drug is administered as the water soluble tromethamine salt and is available in tablets or as an intramuscular injection. The absorption of ketorolac is rapid, Cmax being attained between 20 to 60 min. Its oral bioavailability is estimated to range from 80 to 100%. The drug is extensively bound (>99%) to plasma proteins and has a volume of distri- bution (0.1 to 0.3 L/kg) comparable with those of other NSAIDs. Only small concentrations of ketorolac are detectable in umbilical vein blood after administration to women in labour. The elimination half-life is between 4 and 6h and is moderate in comparison with other NSAIDs. The area under the plasma concentration-time curve of ketorolac is proportional to the dose after intramuscular administration of therapeutic doses to young healthy volunteers. Ketorolac is extensively metabolised through glucuronidation and oxidation; little if any drug is eliminated unchanged. Most of the dose of ketorolac is recovered in the urine as conjugated drug. Although ketorolac is excreted into the breast milk, the amount of drug transferred com- prises only a small fraction of the maternal exposure. Little stereoselectivity was present in the pharmacokinetics of ketorolac in a healthy volunteer receiving single intravenous or oral doses. The elderly exhibit reduced clearance of the drug. Renal insufficiency appears to cause an ac- cumulation of ketorolac in plasma, although hepatic disease may not affect the pharmacokinetics.