Because of widespread (and often uncritical) use of cimetidine. there is considerable potentialfor interactions to occur with other drugs.In studies on absorption. benzylpenicillin absorption was not disturbed by cimetidine in most cases, but a several-fold increase {n'urinary excretion occurred repeatedly in I subJect. indicating that increased absorption of aeld-Iabile compounds may occur in some patients. The absorption of ketoconazole was reduced by more than ha(f with cimetidine. a consequence of its poor water solubility which is enhanced in acid solution. Conflicting results are reported with tetracycline, the overall absorption of which does not appear to be significantly altered by cimetidine. Aspirin absorption was halved by cimetidine in 3 of 6 subjects, when the intragastric pH was raised above 3.5. Cimetidine did not affect the absorption of ampicillin, co-tr/'-moxazole or prednisolone.Cimetidine has been shown to inhibit various microsomal drug-metabolising enzymes in animal as well as human liver, most likely through the binding of the imidazole ring structure qf cimetidine to the haeme moiety qf cytochrome P-450. In 7 studies, cimetidine uniformly prolonged antipyrine haff-life by 18 to 37% and reduced its clearance by 10 to 27%. After chronic dosing with cimetidine, wwfarin clearance was reducedfrom 3.4 to 2.5ml/min, whilst the volume qf distribution and elimination half-life remained unchanged. Steady-state warfarin concentrations, as well as prothrombin times, increased upon addition qf cimetidine to the treatment regimen. Warfarin concentration and effect both returned to pre-cimetidine values when cimetidine was withdrawn. Amongst the benzodiazepines, diazepam, desmethyldiazepam and chlordiazepoxide plasma clearance values were reduced by cimetidine by 43,28 and 63 %, respectively, and half-lives increased accordingly, while volumes of distribution and protein binding were not affected. Long term treatment with cimetidine and diazepam resulted in a 30 to 80 % increase in steady-state diazepam concentrations. In contrast, the pharmacokinetics of oxazepam and lorazepam, which are eliminated almost entirely by glucuronidation and not oxidation, were not altered by cimetidine. Cimetidine also inhibits the metabolism of phenytoin, theophylline and carbamazepine.A single dose of cimetidine decreased indocyanine green clearance by 23 %, which was interpreted as a reduction in hepatic blood flow. The area below the propranolol concentrationtime curve (oral administration) was increased by between 25 and 60 % with cimetidine and by 25 % after intravenous administration of propranolol, with no change in elimination half-life, volume of distribution or bioavailability. With chronic oral propranolol dosing, cimetidine increased the steady-state concentration from 23.2 to 44.9ng/ml. The bioavailability oflabetalol almost doubled from 30 to 54 % with cimetidine, with no change in half-life and systemic