title: The consequences of H2 receptor antagonist--piroxicam coadministration in patients with joint disorders.
abstract: A randomised crossover study was performed in subjects with rheumatoid arthritis (or other arthropathies) to investigate if any alteration in 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 nizatidine. Twelve females and 2 males with mean age, weight, and albumin concentrations of 58 years, 61 kg, and 40 g.L-1 respectively, completed the study. Comparisons were made between the following parameters: plasma piroxicam AUCs [AUC0-24(P)], plasma 5-hydroxypiroxicam AUCs [AUC0-24(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 and after glucuronidase incubation); and the mean of the steady state trough piroxicam, and 5-hydroxypiroxicam concentrations (obtained during each study phase in addition to the wash-out period). A statistically significant difference as a result of initiating either cimetidine or nizatidine was obtained only for the ratio AUC0-23(5-OHP):AUC0-24(P). This was indicative of a weak potential to inhibit piroxicam hydroxylation. No clinically significant alteration in the steady state pharmacokinetics of piroxicam occurred in these subjects as a result of cimetidine or nizatidine coadministration. Consequently it is unlikely that any adverse events would arise from these combinations.
authors.affiliation: Department of Medicine and Therapeutics, Western Infirmary, Glasgow, UK.
authors.forename: P A
authors.initials: PA
authors.lastname: Milligan
authors.forename: P E
authors.initials: PE
authors.lastname: McGill
authors.forename: C W
authors.initials: CW
authors.lastname: Howden
authors.forename: A W
authors.initials: AW
authors.lastname: Kelman
authors.forename: B
authors.initials: B
authors.lastname: Whiting
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001168:Arthritis / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D002927:Cimetidine / Q000009:adverse effects / Q000627:therapeutic use; D004347:Drug Interactions; D005260:Female; D006635:Histamine H2 Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D016567:Nizatidine / Q000009:adverse effects / Q000627:therapeutic use; D010437:Peptic Ulcer / Q000150:complications / Q000188:drug therapy; D010894:Piroxicam / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D006635:Histamine H2 Antagonists; D010894:Piroxicam; D002927:Cimetidine; D016567:Nizatidine