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1. The excretion and metabolism of [2-14C]cimetidine (500mg orally) was studied in five male volunteers.
2. Over 70% of the 14C was excreted in the urine after 24 h by all individuals with 5% in the faeces; 97% being recovered in total after three days.
3. Unchanged cimetidine was the largest urinary component (63%), followed by a polar conjugate tentatively identified as cimetidine N'-glucuronide (24%). Smaller amounts of the oxidized metabolites, cimetidine sulphoxide and 5-hydroxymethylcimetidine, together with the hydrolysis products, cimetidine guanylurea and cimetidine guanidine, were also observed.
4. Cimetidine and its sulphoxide were identified in faecal samples. Anaerobic incubations of cimetidine or cimetidine sulphoxide with faecal homogenates showed that reduction was the predominant reaction under these conditions.
5. Studies in one individual over a wide dose range (0.5 mg to 1.5 g orally) showed little variation in excretory profile or metabolic spectrum.