Influence of cimetidine on the pharmacokinetics of piroxicam in rat and man.

The influence of cimetidine on piroxicam plasma levels and pharmacokinetic parameters was studied in both rats and healthy volunteers. In male rats, intravenous injection of piroxicam (6 mg/kg) in animals pretreated with cimetidine (50 mg/kg intramuscular) resulted in plasma piroxicam concentrations significantly higher than those of animals which received piroxicam alone. The plasma half-life (1/2) of piroxicam in male rats was about 8.3 h and it was increased to 20.74 h by cimetidine pretreatment. The mean area under piroxicam plasma level-time curves was significantly (p less than 0.01) higher in case of rats pretreated with cimetidine compared with those treated with piroxicam alone. Similar results were obtained in male healthy volunteers, where administration of a single dose of piroxicam (20 mg orally) to subjects who received cimetidine (200 mg 3 times a day orally) resulted in plasma piroxicam concentrations significantly higher than those of subjects treated with piroxicam alone. The t1/2 of piroxicam was increased from 37.36 to 52.86 h with cimetidine administration. Also the mean area under piroxicam plasma level-time curves was significantly (p less than 0.05) increased by cimetidine administration.