[H2 antagonists as inhibitors of cytochrome P-450 in rat liver: in vitro and in vivo effects]

Cytochrome P-50 is a well known participant in the metabolism of xenobiotics as well as an activator or inactivator of hepatotoxic substances and carcinogenic agents. H2 antagonists, cimetidine, famotidine and ranitidine were used to inhibit cytochrome P-450 in rat liver. After 200 mg cimetidine, 85% inhibition of cytochrome P-450 in vitro and 50% in vivo were demonstrated through demethylation of aminopyrine. Inhibition was further confirmed by differential absorption spectra (Type II). The percentage inhibition obtained with famotidine or ranitidine were lower than those obtained with cimetidine. Inhibition of the microsomal oxidative system by cimetidine could lead to decreased production of superoxide radicals and protection against damage induced by toxic agents activated in the liver.