ABSTRACT
Background: In therapeutics, the use of Cytochrome P450 inductor and inhibitor can influence the toxicity pattern of Antituberculosis drug in the same patient. Therefore, the study assessed the possible toxicity fate of drug in tuberculosis management following Cytochrome P450 induction and inhibition. Method: Selected and acclimatized albino rats were grouped and administered oral Cimetidine 13.33 mg/kg (inhibitor), Phenobarbitone 10 mg/kg(inducer), Anti-tuberculoid Combination (Pyrazinamide 25 mg/Kg, Rifampicin 10 mg/Kg, Isoniazid 10mg/kg, Ethambutol 15 mg/Kg , and Pyridoxin 10 mg/kg), for twentyeight (28) days. The rats were sacrificed under chloroform anesthesia. Samples were collected and assayed for toxicity markers such as weight, glucose, renal indices, liver indices and hematological indices. Results: Out of thirty-seven (37) toxicities parameters assayed for, eleven (11) toxicities parameters were found to be significantly different (P<0.05). These include weight; (Combination, Combination + Cimetidine), Hematological indices; (Lymphocytes (Cimetidine), platelets (Combination), Mid- range absolute count (Cimetidine, Phenobarbitone, Combination, Combination + Cimetidine) , White Blood Cell (Cimetidine and Combination).Liver indices; alanine transaminase (Cimetidine), Lipid profile (high density lipoprotein( Phenobarbitone, Combination, Combination + Phenobarbitone), very low density lipoprotein ( Phenobarbitone, Combination), cholesterol (Combination), Triglyceride ( Combination), Renal indices: urea (Phenobarbitone, Combination) and sodium ( Cimetidine). There was no mortality recorded at end of 28 days oral drugs administration. Conclusion: The study showed that the inhibition and induction of Cytochrome P450 could influence anti- tuberculoid toxicity. It is therefore, recommended that caution should be built-in the use of antituberculosis medication in patient that has existing seizure, ulcer condition.
