LACK OF EFFECT OF CERTAIN HISTAMINE-H2-RECEPTOR BLOCKERS ON THE GLUCURONIDATION OF 7-HYDROXY-4-METHYLCOUMARIN BY HUMAN LIVER-MICROSOMES

Contrary to the general belief that cimetidine and ranitidine spare glucuronidation of drugs, some authors have indicated that both cimetidine and ranitidine could inhibit the glucuronidation of paracetamol (acetaminophen) by cultured rat hepatocytes. Thus, we tested the effect of three histamine H-2-receptor blockers (cimetidine, ranitidine and famotidine) on the glucuronidation of 7-hydroxy-4-methylcoumarin (7-OH-4-MC) by human liver microsomes. None of the drugs studied produced significant inhibition of the glucuronidation of 7-OH-4-MC when used at concentrations up to 1.5 mM. Thus, even the new H-2-receptor blocker, famotidine, spares glucuronidation. These findings further support the previous reports which suggest that glucuronide conjugation in humans is spared by H-2-receptor blockers.