title: Inhibition of drug metabolism by cimetidine in man: dependence on pretreatment microsomal liver function.
abstract: The effect of cimetidine on hepatic microsomal drug metabolism was studied in six patients with normal liver and eleven patients with chronic liver disease using the aminopyrine breath test. Before administration of cimetidine, the elimination rate constant of 14CO2 from breath (Kb) was 28.3 +/- SD 1.3%/h in patients with normal liver and 13.5 +/- 7.7%/h in patients with liver disease (P less than 0.001). After 7 days of cimetidine therapy (1 g/day) Kb decreased to 23.3 +/- 5.2%/h (19.0 +/- 13.8% decrease; P less than 0.05) and 7.4 +/- 5.8%/h (50.5 +/- 14.4% decrease; P less than 0.001), respectively. Plasma levels of cimetidine were not significantly different (1.05 +/- 0.14% micrograms/ml v. 0.88 +/- 0.41; P greater than 0.05). The findings indicate that therapeutic doses of cimetidine lead to an inhibition of drug metabolism which is more pronounced in patients with impaired liver function than in liver normals. Therefore, patients with chronic liver disease may be at increased risk with respect to interactions between cimetidine and other drugs which are demethylated by the liver.
mesh_terms: D000368:Aged; D000632:Aminopyrine / Q000378:metabolism; D001944:Breath Tests; D002908:Chronic Disease; D002927:Cimetidine / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D003864:Depression, Chemical; D005260:Female; D006146:Guanidines / Q000009:adverse effects*; D006801:Humans; D007677:Kidney Function Tests; D007700:Kinetics; D008107:Liver Diseases / Q000188:drug therapy / Q000378:metabolism; D008111:Liver Function Tests; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008745:Methylation; D008862:Microsomes, Liver / Q000187:drug effects*; D008875:Middle Aged; D013997:Time Factors
chemical_list: D006146:Guanidines; D000632:Aminopyrine; D002927:Cimetidine