Ranitidine treatment inducing methemoglobinemia in male Wistar rats

Abstract

Drug idiosyncrasy is an adverse event of unknown etiology that occurs in a small fraction of people taking a drug. The histamine-2 (H2)-receptor antagonist ranitidine causes idiosyncratic reactions in patients. To investigate the hypothesis that ranitidine could induce hematological toxic effects, the drug was administered intraperitoneally (ip) to two of six groups of 200-220 g male Wistar rats (n=6). Group I received as single dose of saline solution (NaCl, 200 µL) Group II received 200 µL of NaCl, ip, at 0, 24, 48 and 72 h, Group III (controls of the vehicle) received as single dose of dimethyl sulfoxide (DMSO, 200µL), ip, Group IV (controls of the vehicle) received 200 µL of DMSO, ip, at 0, 24, 48, and 72 h, Group V received a single dose of 100 mg/kg of ranitidine in 200 µL of DMSO) ip, Group VI received 50 mg/kg of ranitidine, in 200 µL of DMSO, ip, at 0, 24, 48, and 72 h. Erythrograms, leucograms were measured; percent methemoglobin content of the blood was analyzed spectophotometrically. Methemoglobinemia increased to a significant extent following ranitidine treatment, in both study groups. White blood cell and neutrophil counts showed a discrete reduction following either regime of treatment. A marginal mobilization of the neutrophil pool probably occured. Following the multiple dose regime, leukocyte counts increased, but their distribution maintenance profile remained the same. The administration of ranitidine to rats induces methemoglobinemia in the administered doses, suggesting that from a certain concentration and dosage scheme the substance can be methemeglobinemia inductor.