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 H2-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 H2-receptor blocker, famotidine, spares glucuronidation. These findings further support the previous reports which suggest that glucuronide conjugation in humans is spared by H2-receptor blockers.
Irshaid
Y
Y
Department of Pharmacology, Faculty of Medicine, Jordan University of Science and Technology, Irbid.
Abu-Khalaf
M
M
D002927:Cimetidine / Q000494:pharmacology; D015738:Famotidine / Q000494:pharmacology; D014453:Glucuronosyltransferase / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D006801:Humans; D006923:Hymecromone / Q000031:analogs & derivatives* / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D011899:Ranitidine / Q000494:pharmacology; D014535:Uridine Diphosphate Glucuronic Acid / Q000378:metabolism
D006635:Histamine H2 Antagonists; D014535:Uridine Diphosphate Glucuronic Acid; D006923:Hymecromone; D015738:Famotidine; C034888:4-methylumbelliferyl glucuronide; D002927:Cimetidine; D011899:Ranitidine; D014453:Glucuronosyltransferase