EXPERIMENTAL STUDIES ON THE ANALGESIC AND ANTIPYRETIC EFFECTS OF IBUPROFEN COMBINED WITH 18 β-GLYCYRRHETINIC ACID

The supplementation of NSAIDs with adjuvants that alleviate their adverse effects is considered advantageous. Ibuprofen is a typical COX inhibitor, commonly used as an effective analgesic/antipyretic drug. 18 beta-glycyrrhetinic acid was reported to inhibit lipoxygenase, to have protective effect against stomach and liver damage in rats. To study the analgesic and antipyretic effect of combined therapy with ibuprofen plus 18 beta-glycyrrhetinic acid on carrageenan induced hyperalgesia and experimental febrile reaction in rats groups of ten. male Wistar rats each were treated per os with 18 beta-glycyrrhetinic acid (10 mg/ml/kg), ibuprofen (10, 20 and 40 mg/ml/kg) or a combination of them. Inflammatory hyperalgesia was induced by intraplantar injection of 1% carrageenan. Rectal temperature was measured before and 3, 4, 5, 5.5, 6 and 7 h after induction of the febrile reaction (20% brew yeast, s.c.). The levels of PgE(2) released in vitro by isolated brain cortical slices were determined by radioimmunoassay. Treatment with 18 beta-glycyrrhetinic acid (10, 20 mg/kg) did not change significantly the pain threshold. Co-treatment with ibuprofen (20 mg/kg) and 18 beta-glycyrrhetinic acid (10 mg/kg) increased the analgesic activity at 120 min. 18 beta-glycyrrhetinic acid (10 mg/kg) showed moderate, but significant antipyretic activity (7th hour after yeast febrile induction). Ibuprofen (10, 20 mg/kg) showed significant antipyretic activity. Ibuprofen (40 mg/kg) prevented the increase of body temperature by yeast injection. Combination of 18 beta-glycyrrhetinic acid (10 mg/kg) with ibuprofen (10 mg/kg) resulted in significantly stronger antipyretic effect. Combination of ibuprofen (20 mg/kg) and 18 beta-glycyrrhetinic acid (10 mg/kg) resulted in a stronger prevention of increased body temperature similar to the effect of 40 mg ibuprofen. Ibuprofen and 18 beta-glycyrrhetinic acid decreased in vitro levels of Pg E(2). It was concluded that 18 beta-glycyrrhetinic acid could be a useful supplement of antipyretic and analgesic drugs against different febrile reactions and pain conditions.