title: Clinical pharmacology of tolmetin: comparisons in rheumatoid arthritis patients and normal volunteers.
abstract: The pharmacokinetics of tolmetin sodium were studied in five patients with rheumatoid arthritis (RA) and five normal volunteers to determine whether data derived from normals could be applied to RA patients. In addition, prostaglandin E (PGE) levels in synovial fluid were compared with tolmetin levels in serum and synovial fluid. Both groups received 400 mg tolmetin every 6 hours for seven days. During a 24-hour washout period after the dose of tolmetin (400 mg) on day 8, blood and urine samples were obtained from all study participants, and synovial fluid samples from the RA patients only. The patients continued into a second 24-hour drug-free period, after which they received a single 400-mg dose of tolmetin. Blood and urine samples were again collected. No clinically or statistically significant differences in tolmetin kinetics between normal volunteers and RA patients were found. A comparison of multiple-dose and single-dose results in the patient group showed an 11 per cent increase in the tolmetin serum concentration after multiple dosing. Total PGE levels in synovial fluid remained significantly depressed in the patient group for 24 hours after the 400-mg test dose of tolmetin on day 8. These findings suggest that tolmetin serum kinetics may not be an appropriate indicator of the duration of biologic activity of tolmetin.
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D001682:Biological Availability; D005260:Female; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011458:Prostaglandins E / Q000378:metabolism; D011758:Pyrroles / Q000627:therapeutic use*; D013582:Synovial Fluid / Q000378:metabolism; D014046:Tolmetin / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D011458:Prostaglandins E; D011758:Pyrroles; D014046:Tolmetin