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  • Title: The effect of cimetidine and ranitidine on paracetamol glucuronidation and sulphation in cultured rat hepatocytes.
    Author: Emery S, Oldham HG, Norman SJ, Chenery RJ.
    Journal: Biochem Pharmacol; 1985 May 01; 34(9):1415-21. PubMed ID: 3994756.
    Abstract:
    Cimetidine and ranitidine have been investigated for their ability to inhibit conjugation reactions in cultures of rat hepatocytes. Neither compound had any appreciable effect on rates of paracetamol sulphation. However, both cimetidine and ranitidine inhibited the glucuronidation of paracetamol in a dose-dependent manner. No adverse effects on cellular viability were noted utilizing enzyme leakage (lactic dehydrogenase) or protein synthesis measurements. The kinetics of inhibition by ranitidine were studied in more detail. At 0.25 mM ranitidine, the inhibition appeared to be purely competitive. However, at higher concentrations decreases in Vappmax were noted suggesting a more complex mechanism of inhibition. The relevance to inhibition in vivo by cimetidine and ranitidine and possible interactions between paracetamol and these histamine H2-receptor antagonists are discussed.
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