The antinociceptive and anti-inflammatory effects of five depot formulations of ketorolac propyl ester in rats.
BACKGROUND
Ketorolac is a potent nonsteroidal anti-inflammatory drug. Recently, a ketorolac prodrug, ketorolac propyl ester, was synthesized in our laboratory. The aim of the study was to evaluate the antinociceptive and anti-inflammatory effects of ketorolac propyl ester in five depot formulations. The vehicles used in these formulations were injectable vegetable oils, i.e., sesame oil, peanut oil, soybean oil, castor oil, and cottonseed oil. The traditional therapentic form of ketorolac tromethamine in saline was used as control.


METHODS
Six studies were carried out to test the antinociceptive and anti-inflammatory effects of intramuscular ketorolac tromethamine (in saline) and its propyl ester (in five depot formulations) 240 micromol/kg on Sprague-Dawley rats treated with intraplantar carrageenin.


RESULTS
Ketorolac tromethamine (in saline) produced an 8 h duration of action on both antinociception and anti-inflammation, whereas ketorolac propyl ester in five oily vehicles produced 54- to 78-h durations of actions in both antinociception and anti-inflammation. Ketorolac propyl ester in cottonseed oil produced a duration of action of 78h in both antinociception and anti-inflammation.


CONCLUSIONS
All five depot formulations of ketorolac propyl ester produced longer durations of antinociceptive and anti-inflammatory effects.
Wang
Li-Kai
LK
Departments of Anesthesiology and Medical Research, Chi-Mei Medical Center, Yung-Kang and Liou-Ying, Taiwan, ROC.
Wang
Pei-Jung
PJ
Hou
Chia-Hui
CH
Chu
Chin-Chen
CC
Tzeng
Jann-Inn
JI
Shieh
Ja-Ping
JP
Wang
Jhi-Joung
JJ
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical; D020910:Ketorolac / Q000494:pharmacology*; D020911:Ketorolac Tromethamine / Q000494:pharmacology*; D008297:Male; D010938:Plant Oils / Q000008:administration & dosage; D011355:Prodrugs / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D010938:Plant Oils; D011355:Prodrugs; D020911:Ketorolac Tromethamine; D020910:Ketorolac