THE CONSEQUENCES OF H-2-RECEPTOR ANTAGONIST PIROXICAM COADMINISTRATION IN PATIENTS WITH JOINT DISORDERS

A randomised crossover study was performed in subjects with rheumatoid arthritis (or other arthropathies) to investigate if any alteration i n the steady pharmacokinetics of the NSAID piroxicam (a drug which is extensively metabolised via cytochrome P450) or its major metabolites occurred as a result of coadministering either cimetidine or nizatidin e. Twelve females and 2 males with mean age, weight, and albumin conce ntrations of 58 years, 61 kg, and 40 g . L-1 respectively, completed t he study. Comparisons were made between the following parameters: plas ma piroxicam AUCs [AUC0-24(P)], plasma 5-hydroxypiroxicam AUCs [AUC0-2 4(5-OHP)], the ratio of these i. e. AUC0-24(5-OHP): AUC0-24(p), the % piroxicam daily dose excreted in urine as 5-hydroxypiroxicam (before a nd after glucuronidase incubation); and the mean of the steady state t rough piroxicam, and 5-hydroxypiroxicam concentrations (obtained durin g each study phase in addition to the wash-out period). A statisticall y significant difference as a result of initiating either cimetidine o r nizatidine was obtained only for the ratio AUC0-23(5-OHP): AUC0-24(p ). This was indicative of a weak potential to inhibit piroxicam hydrox ylation. No clinically significant alteration in the steady state phar macokinetics of piroxicam occurred in these subjects as a result of ci metidine or nizatidine coadministration. Consequently it is unlikely t hat any adverse events would arise from these combinations.