ABSTRACT

Background: Drug therapies of an existing disease can influence the toxicity pattern of a newly diagnosed disease in a patient. The study therefore assessed the pattern of antibacterial combination toxicity following CYP450 inhibition/induction in albino rat.

Method: Selected acclimatized adult albino rats were grouped and administered oral cimetidine (13.33mg/kg), phenorbarbitone (10 mg/kg), cefixime+clavulanic acid (6.66 mg/kg) for a period twenty eight (28) days , The animals were sacrificed under chloroform anaesthesia and assayed for haematological ,renal, liver enzyme, lipid ,and weight indices as toxicity markers.

Results: Out of the thirty seven (37) indices assayed, twelve(12) were found to be significantly different, they include Weight (combination + cimetidine P<0.O5) , haematological ( white blood cell (cimetidine , combination,combination + cimetidine,combination + phenobarbitone P<0.O5), granulocyte (cimetidine P<0.O5 ), mid-range absolute control (cimetidine , combination,combination + cimetidine,combination P<0.O5) , Mean Corpuscular Haematocrit ( cimetidine versus combination +phenorbarbitone , percentage Lymphocyte (cimetidine , combination + cimetidine P<0.O5) ,Haemoglobin (cimetidine versus combination +phenobarbitone P<0.O5) , liver enzymes (Alanine Transaminase(cimetidine , combination + phenobarbitone P<0.O5) , Lipid indices (High Density Lipoprotein (cimetidine,phenobarbitone,combination ,combination +cimetidine P<0.O5)), Renal indices( Urea (cimetidine versus phenobarbitone ,combination P<0.O5) ,Sodium(cimetidine P<0.O5) ,Potassium (combination versus cimetidine versus cimetidine , phenobarbitone , combination versus phenobarbitone P<0.O5)). No mortality was recorded in all the groups.

Conclusion: In the forgoing, CYP450 inhibition/induction have altered the toxicity markers in a co-existing disease condition. Therefore caution should be built in the use of antibacterial agents in patients that has existing ulcer/seizure condition.