Evaluation of gastric tolerability, antinociceptive and antiinflammatory activity of combination NSAIDs in rats.

Background: Non-steroidal antiinflammatory drugs (NSAIDs) are one of the most commonly prescribed drugs in clinical practice. Presently, several varieties of fixed dose combinations (FDCs) of NSAIDs are available over the counter and are being prescribed too. There is paucity of literature regarding comparative efficacy of these combinations against their individual component. Various clinical studies have documented increased incidence of gastric ulcerations with usage of more than one NSAID simultaneously.

Objectives: To study gastric tolerability, antinociceptive and antiinflammatory activity of combination NSAIDs in rats.

Materials And Methods: Gastric tolerability of different NSAIDs was observed after administration of drugs for 7 days orally. On 7 th day, 4 h after drug administration, rats were sacrificed and stomach mucosa was examined for ulcerations. Analgesic or antinociceptive activity of single and combination NSAIDs was evaluated using Writhing test model. For induction of writhing, 4% normal saline (hypertonic saline) was injected (0.1 ml/10 gm) intraperitoneally. Evaluation of antiinflammatory activity for FDCs of NSAIDs was done by using rat paw edema model with the aid of plethysmometer. Paw edema was induced by injecting 0.1 ml of 1% formalin in sub-planter region of hind paw.

Results: Analgesic activity was found to be enhanced or significant only in the group pretreated with combination of nimesulide with ibuprofen as compared to ibuprofen-alone group (P = 0.01). Decrease in mean paw edema (antiinflammatory activity) was not significant in rats pretreated with combination NSAIDs as compared to NSAID-alone group. Mean gastric ulcer index was significant in groups pretreated with diclofenac alone (P = 0.03) and in combination groups of nimesulide with diclofenac and ibuprofen with paracetamol as compared to control (P = 0.03, P = 0.007).

Conclusion: Addition of ibuprofen to paracetamol and combining diclofenac to nimesulide, significantly increased severity of gastric ulcerations. Fixed dose combination does not possess additional analgesic activity over their individual components, only exception being combination of nimesulide with ibuprofen, which has additional analgesic activity over ibuprofen alone, and this combination was not found to be ulcerogenic. Antiinflammatory activity of ibuprofen, paracetamol and nimesulide was significantly enhanced after addition of diclofenac.