Modification of antiinflammatory, antipyretic and analgesic effects of celecoxib with some antiulcer drugs in experimental animals

ABSTRACT

Patients under antiulcer therapy may suffer from a concurrent disease which requires the use of one of NSAIDs, In such cases, these patients are likely to receive a combination of one of the antiulcer drugs plus the NSAIDs. Accordingly, the simultaneous use of one of the NSAIDs with one of the antiulcer drugs may lead to drug-drug interaction. The present work was devoted to the assessment of the modification of the anti-inflammatory, antipyretic and analgesic effects of celecoxib after the concurrent administration of the antiulcer drugs, omeprazole and ranitidine. This study was performed on two animal species, rats and mice. Rats were used to detect the anti-inflammatory and the antipyretic activities of the investigated drugs. Mice were utilized to study the analgesic activity of the same drugs.Male albino rats were divided into 2 main groups Group I. rats were divided into 5 subgroups, to study the anti-inflammatory activity of the tested drugs by induction of inflammation by subcutaneous injection of 0.1 ml of 20% brewer's yeast suspension into planter surface of the right hid paw and measuring the rats paw thickness according to the treatment received. Group II rats were divided into 5 subgroups, to study the anti-pyretic activity of the tested drugs by induction of pyrexia by subcutaneous injection of 2.5ml of 20% aqueous suspension of yeast dorsally and ventrally and recording the rectal temperature according to the treatment received. GroupIII mice were divided into two set of experiment each of which divided into 5 subgroups. The analgesic activity of the drugs was evaluated by chemical method [p-benzoquinon induced -writhing response and the thermal method [hot plate method]. Intraperitoneal [i.p.] administration of celecoxib produced highly significant reduction in the rat's paw edema. Intraperitoneal injection of celecoxib and ranitidine caused highly significant decrease in the rat's paw edema. Similarly the combined i.p injection of celecoxib and omeprazole gave a highly significant reduction in the rat's paw edema. Intraperitoneal administration of celecoxib Into hyper-thermic rats led to a remarkable reduction in body temperature of rats. Combined administration of celecoxib and ranitidine produced highly significant decrease in body temperature. The combined i.p administration of celecoxib and omeprazole caused a highly significant decrease. In body temperature. The i.p administration of celecoxib before the injection of P-benzoquinon [PBQ] protected the animals against writhing response. Intraperitoneal injection of celecoxib and ranitidine resulted in protection of animals from PBQ-induced writhing response which was highly significant. The simultaneous administration of celecoxib and omeprazole protected the animals from PBQ-induced writhing response which was highly significant. Intraperitoneal injection of celecoxib revealed a highly significant increase in the reaction time. The combined administration of celecoxib and ranitidine caused highly significant increase in the reaction time. Intraperitoneal administration ofcelecoxib and omeprazole also produced highly significant increase in the reaction time to thermal stimulus. Intraperitoneal injection of ranitidine or omeprazole caused non significant change in the rat's paw edema or yeast induced pyrexia, but ranitidine caused a significant decrease in PBQ-induced writhing response and in hoi plate-induced pain. On the other hand omeprazol produced non significant change in PBQ-induced writhing response and in hot plate-induced pain. It could be suggested that ranitidine is a relatively better drug than omeprazole with respect to anti-inflammatory, antipyretic and analgesic actions when used concurrently with a selective COXII inhibitor