Late benign intrathoracic gastric perforation after oesophagectomy for carcinoma.

Cimetidine interaction with phenytoinCimetidine inhibits the hepatic microsomal oxidation system in vitro and reduces clearance of drugs metabolised by these enzymes.'In man cimetidine increases the effect of warfarin'' and diazepam.4Phenytoin, a commonly used anticonvulsant with a narrow therapeutic index, is also metabolised by the hepatic microsomal system.We therefore investigated the effect of cimetidine on steady-state plasma phenytoin concentrations in patients with longstanding epilepsy.Patients studied and mean serum phenytoin concentrations ( SD) before, during, and after cimetidine (C) Phenytoin Mean plasma phenytoin (gmol/l)* Case Age dose Other drugs No (years) (mg/day) Before C During C After C 1 27 400 Carbamazepine 74-7±5-8 99-2±6-3t 89-4±11-0 2 20 260 Valproate, primidone 63-8 ±3-1 82-6±6-7t 74-5 ±2-1 3 33 300 Clonazepam, primidone 45-4±39 527 ±4-5t 48-0±0-7 4 63 300 Phenobarbitone 33-8±3-8 40-3±3-5t36-0±0 0 *Therapeutic range ,umol/l (10-20 ,ug/ml). tp <002 compared with value before cimetidine.Conversion: SI to traditional units-Phenytoin: 1 ,umol/l 0-25 ,g/ml.in free urinary phenytoin would be consistent with this.Alternatively, but less likely, cimetidine may have caused an increase in phenytoin bioavailability.Cimetidine and phenytoin are often prescribed, and concurrent administration will therefore occur in some patients.Our findings show that caution is necessary when adding cimetidine to phenytoin treatment, especially when plasma concentrations are already in the upper therapeutic range.