Metabolism of cimetidine

It is important to study the metabolism of any new drug in case the metabolites have biological activity in their own right. Any such activity might lead to side-effects. Alternatively, a metabolite might have enhanced activity of the type desired and give clues to further development. 

Cimetidine itself is metabolically stable and is excreted largely unchanged. The only metabolites which have been identified are due to oxidation of the sulfur link (Fig. 13.40) or oxidation of the ring methyl group (Fig. 13.41). 

It has been found that cimetidine inhibits the P-450 cytochrome oxidase system in the liver. This is an important enzyme system in the metabolism of drugs and care must be taken if other drugs are being taken at the same time as cimetidine, since 

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Caution is needed to avoid potential drug interactions. Tamsulosin decreases metabolism of cimetidine and diltiazem. Carbamazepine and phenytoin increase catabolism of a-adrenergic antagonists. 

Rennick B, Ziemniak J, Smith I, Taylor M, Acara M. Tubular transport and metabolism of cimetidine in chicken kidneys. J Pharmacol Exp Ther 1984 228 387-392. 

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