Effect of cimetidine and ranitidine on the metabolism and toxicity of hexamethylmelamine.
In a rat model, doses of 20-120 mg/kg of cimetidine prolonged in a dose-related manner the half-life of hexamethylmelamine by 29%-80%, while doses of 1-25 mg/kg of ranitidine did not. Administration of 120 mg/kg of cimetidine with a single 350-mg/kg dose of hexamethylmelamine increased toxicity from LD30 to LD75 (P = 0.005). When combined with 25 mg/kg of ranitidine, a statistically insignificant (P = 0.16) 15% increase in hexamethylmelamine toxicity was noted. These studies indicate that cimetidine but not ranitidine increases the toxicity of hexamethylmelamine through inhibition of microsomal metabolism.
D006585:Altretamine / Q000378:metabolism* / Q000633:toxicity; D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D002927:Cimetidine / Q000494:pharmacology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D011899:Ranitidine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014227:Triazines / Q000378:metabolism*
D014227:Triazines; D000632:Aminopyrine; D002245:Carbon Dioxide; D002927:Cimetidine; D011899:Ranitidine; D006585:Altretamine