Clinical Pharmacokinetics of Ketorolac Tromethamine
- 103 Downloads
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 distribution (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 comprises 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 accumulation of ketorolac in plasma, although hepatic disease may not affect the pharmacokinetics.
KeywordsWarfarin Ketoprofen Ketorolac Clinical Pharmacokinetic Plasma Protein Binding
Unable to display preview. Download preview PDF.
- Anonymous. Toradol prescribing information. Syntex Inc. and Upjohn Co. of Canada. 1991Google Scholar
- D’Arienzo M, Pennisi M, Zanolo G, Borsa M. Ketoprofen lysine: ketoprofen serum levels and analgesic activity. Drugs in Experimental Clinical Research 10: 863–866, 1984Google Scholar
- Bach AJ, Lavelle CJ, Olander KW, Retzlaff JA, Sorenson LW. The effect of ketorolac tromethamine solution 0.5% in reducing postoperative inflammation after cataract extraction and intraocular lens implantation. Ophthalmology 95: 1279–1284, 1988Google Scholar
- Jamali F, Pasutto FM, Lemko C. HPLC of ketorolac enantiomers and application to pharmacokinetics in the rat. Journal of Liquid Chromatography 12: 1835–1850, 1989bGoogle Scholar
- Martinez J, Garg DC, Pages LJ, Jallad NS, Yee JP, et al. Single dose pharmacokinetics of ketorolac in healthy young and renal impaired subjects. Abstract No. 72. Journal of Clinical Pharmacology 27: 722, 1987Google Scholar
- Mroszczak EJ, Ling T, Yee J, Massey I, Sevelius H. Ketorolac tromethamine absorption and pharmacokinetics in humans. Clinical Pharmacology and Therapeutics 37: 215, 1985Google Scholar
- Pages LJ, Martinez JJ, Garg DC, Yee JP, Mroszczak J, et al. Pharmacokinetics of ketorolac tromethamine in hepatically impaired vs young healthy subjects. Abstract No. 78. Journal of Clinical Pharmacology 27: 724, 1987Google Scholar
- Resman-Targof TBH. Ketorolac: a parenteral nonsteroidal antiinflammatory drug. Drug Intelligence and Clinical Pharmacy 24: 1098–1104, 1990Google Scholar
- Reynolds J. (Ed.) Analgesic and antiinflammatory drugs. In: Martindale the extra pharmacopoeia, 29th ed., pp. 1–46, Pharmaceutical Press, London, 1989Google Scholar
- Rooks WH II, Maloney PJ, Shott PJ, Schuler ME, Sevelius H, et al. The analgesic and anti-inflammatory profile of ketorolac and its tromethamine salt. Drugs in Experimental Clinical Research 11: 479–492, 1985Google Scholar
- Townsend RJ, Benedetti TJ, Erickson SH, Cengiz C, Gillespie WR, et al. Excretion of ibuprofen into breast milk. American Journal of Obstetrics and Gynaecology 149: 184–186, 1984Google Scholar
- Wilson SJ, Errick JK, Balkon J. Pharmacokinetics of nalbuphine during parturition. American Journal of Obstetrics and Gynaecology 155: 340–344, 1986Google Scholar
- Wu AT, Huang BL, Massey IJ, Kushinsky S. Quantification of ketorolac in plasma and aqueous humor by high performance liquid chromatography. American Pharmaceutical Association Abstracts 16: 145, 1986Google Scholar