Equivalent Intraperitoneal to Orally Administered Doses of Ibuprofen on Dose Response Curve for Analgesia and Prostaglandin Inhibitory Effect in Mice

Abstract

Ibuprofen is used chronically in different animal models of inflammation, by administration in drinking water or in diet due to its short half life. Though this practice has been used for years, ibuprofen doses were never assayed against parentral dose response curves. This study aims at identifying the equivalent intraperitoneal dose of ibuprofen administered in drinking water or in diet. Bioassays were performed using formalin test and incisional pain model for analgesic efficacy and spinal PGE2 and serum TXB2 for eicosanoide inhibitory activity. The dose response curve of i.p. ibuprofen was constructed for each test using 50, 75, 100 and 200 mg/kg BW. The assayed ibuprofen concentrations in drinking water were 0.2, 0.35, 0.6 mg/ml and in diet were 82, 263, 375 mg/kg diet. These doses are commonly used in literature. Phase 2a of the formalin test (the most sensitive phase to COX inhibitory agents) showed that the 3 doses applied in drinking water and those administered in diet lied between 65 and 85 mg/kg BW, i.p. Area between the mechanical threshold time curves in incisional pain model showed that the 3 doses applied in drinking water and those applied in diet lied between 50 and 80 mg/kg BW, i.p. On spinal PGE2 inhibitory response curve, the 3 doses applied in drinking water and those administered in diet lied between 70 and 95 mg/kg BW, i.p. On Serum TXB2 inhibitory response curve the 3 doses applied in drinking water and those administered in diet lied between 65 and 125 mg/kg BW, i.p. Conclusion: The increment in pharmacologic effects of different doses of continuously administered ibuprofen in drinking water or diet do not parallel those administered i.p. Equivalent i.p. doses were not similar in the four tests performed in the present study, with those of surgical pain model being lower than other assays. It is difficult to assume these equivalent doses based on mathematical calculations.