title: Novel depots of ketorolac esters have long-acting antinociceptive and antiinflammatory effects.
abstract: No long-acting nonsteroidal antiinflammatory drug is clinically available for the treatment of pain. In this study, we evaluated the antinociceptive and antiinflammatory effects and duration of action of several novel depots of ketorolac esters, such as ketorolac propyl ester, pentyl ester, heptyl ester, and decyl ester, and observed whether they had a long-acting effect. Four studies in Sprague-Dawley rats were performed. In Studies 1-3, the antinociceptive and antiinflammatory effects of IM ketorolac tromethamine and its base and propyl ester were evaluated. In Study 4, the antinociceptive and antiinflammatory effects of several other ketorolac esters were evaluated. We found that ketorolac tromethamine 24, 80, and 240 micromol/kg (in saline) produced significant antinociceptive and antiinflammatory effects with duration of action of approximately 6-8 h. The four ketorolac esters at a dose of 240 micromol/kg (in oil) produced significant long-acting antinociceptive and antiinflammatory effects, with duration of action of approximately 52-76 h. We concluded that IM injection of novel depots of ketorolac esters in rats produce long-acting antinociceptive and antiinflammatory effects that are 6.5- to 9.5-fold longer than the traditional dosage form of ketorolac tromethamine.
authors.affiliation: *Department of Oral and Maxillofacial Surgery, National Defense Medical Center, Taipei; †Department of Oral and Maxillofacial Surgery, Taipei Medical University, Taipei; and ‡Departments of Anesthesiology and Medical Research, Chi-Mei Medical Center, Tainan (Yung-Kang and Liou-Ying), Taiwan.
authors.forename: Shyun-Yeu
authors.initials: SY
authors.lastname: Liu
authors.forename: Ja-Ping
authors.initials: JP
authors.lastname: Shieh
authors.forename: Jann-Inn
authors.initials: JI
authors.lastname: Tzeng
authors.forename: Hou
authors.initials: H
authors.lastname: Chia-Hui
authors.forename: Yen-Ling
authors.initials: YL
authors.lastname: Cheng
authors.forename: Kuo-Lun
authors.initials: KL
authors.lastname: Huang
authors.forename: Jhi-Joung
authors.initials: JJ
authors.lastname: Wang
mesh_terms: D000700:Analgesics / Q000008:administration & dosage* / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000494:pharmacology*; D002351:Carrageenan; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D007273:Injections, Intramuscular; D020911:Ketorolac Tromethamine / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000494:pharmacology*; D008297:Male; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D020911:Ketorolac Tromethamine; D002351:Carrageenan