The Protective Effect of Cimetidine on Dapsone Induced Haemotoxicity in Rats

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Sebha University
Dapsone is a drug that is effectively used in the treatment of a variety of infectious diseases such as leprosy and malaria, also in inflammatory disorders like dermatitis herpetiformis. The N-hydroxylated metabolites of dapsone are responsible for most of its adverse reactions. The present study aims to evaluate the role of one of the inhibitors of oxidative metabolism, cimetidine, on dapsone induced haemotoxicity in rats. The treated experimental animals were divided into 4 groups. The first and third groups were receiving a dose of 10mg/Kg dapsone alone by gavage once and twice daily respectively for 4 weeks. The second and fourth groups were dosed as in the first and third groups, except that cimetidine (40 mg/Kg) was given by gavage one hour before each dapsone dose. The results of the study revealed significant increase in met Hb% in dapsone treated groups compared with the control group, which was dose-dependent (12.73 ± 1.79 and 26.22 ± 2.87 in the first and third groups respectively). There was significant decrease in met Hb% of the second group compared with the first group (3.80J± 0.8 Vs 12.73 ± 1.7i)) which could be attributed to the metabolic inhibitory effect of cimetidine. With higher doses of dapsone, cimetidine did not have the same metHb reduced effect as metHb was insignificantly decreased in the fourth group compared with the third group (23.59 ± 3.36 Vs 26.22 ± 2.87). There was also significant reduction in haemoglobin and red blood cell count (haemolysis) and neutrophil count (agranulocytosis) in dapsone treated groups, which was dose dependent and not alleviated by co-administration of cimetidine. From the study, it can be concluded that although cimetidine may reduce metHb formation during prolonged dapsone administration, dose reduction of dapsone is required to avoid haemotoxicity because of the increased accumulation of both parent drug and its metabolites. Also, one should take care about "therapy efficiency/ adverse effect" balance using the correct dose, monitoring relevant clinical and laboratory parameters and educating patients.