Disease relevance of tolmetin

• Anaphylaxis from tolmetin [1].
• Tolmetin and agranulocytosis [2].
• Nephrotic syndrome induced by tolmetin [3].
• Tolmetin. Association with reversible renal failure and acute interstitial nephritis [4].
• Tolmetin-induced aseptic meningitis [5].

High impact information on tolmetin

• The new antirheumatic agents, fenoprofen calcium, naproxen, and tolmetin sodium, are effective in the management of rheumatoid arthritis [6].
• In this paper we describe the use of tandem mass spectrometry to locate binding sites and elucidate the binding mechanism involved in the formation of covalent adducts from tolmetin glucuronide and albumin in vitro [7].
• Proteinuria associated with tolmetin treatment in a patient with systemic lupus erythematosus [8].
• Tolmetin-induced thrombocytopenia [9].
• The protein adduct exhibited an average half-life of 4.8 +/- 0.9 days in contrast to the much shorter 5-hour half-lives for tolmetin and its glucuronide [10].

Chemical compound and disease context of tolmetin

• In a single-blind crossover study, five healthy volunteers who had previously developed erosive gastritis secondary to one week of aspirin therapy were randomly assigned to seven-day courses of treatment with ibuprofen, tolmetin and placebo [11].
• Several additional amino acid amides of tolmetin were similar to the glycine amide in exhibiting increased potency and reduced gastrointestinal toxicity in comparison to equivalent doses of tolmetin sodium [12].
• A double-blind comparative evaluation of tolmetin versus naproxen in osteoarthritis [13].
• The results of this study suggest that whilst tolmetin and sulindac may be beneficial for patients suffering from depression, these agents also have the potential to induce adverse effects in patients suffering with neurological disorders such as Parkinson's disease [14].
• Pertussis toxin (50 micrograms/l) did not modify the effect of indometacin, mefenamic acid, and tolmetin, but partially antagonized the effects of diclofenac and naproxen and increased the effect of phenylbutazone and piroxicam [15].

Biological context of tolmetin

• The pharmacokinetics and irreversible plasma protein binding of tolmetin were studied in six healthy subjects after the administration of a single, 400 mg dose of tolmetin [16].
• Disposition and irreversible plasma protein binding of tolmetin in humans [16].
• Tolmetin kinetics were determined in the plasma and synovial fluid of five rheumatoid arthritis patients after they had ingested tolmetin (400 mg every 6 hr) for 7 days [17].
• The absorption, kinetics, biotransformation, and excretion of tolmetin and its metabolites were studied in patients with rheumatoid arthritis (RA) to evaluate the effects of the disease on tolmetin disposition [18].
• NSAID (indomethacin, 3 mg/kg; tolmetin, 10 mg/kg; phenoxybenzamin, 10 mg/kg; aspirin, 100 mg/kg) increased plasma volume and extracellular fluid volume of rats after repeated medication for 3 or 5 days, but the body fluid volume expansion disappeared with further repeated administration of NSAID [19].

Anatomical context of tolmetin

• The average half-lives of tolmetin in plasma and synovial fluid were 6.77 +/- 1.47 hr and 6.90 +/- 2.3 hr [17].
• Distribution of tolmetin in the whole blood of 8 healthy subjects using a centrifugation technique showed that the drug was not taken up by red blood cells at therapeutic concentrations [20].
• 6 From these results, it is concluded that the site of anti-writhing action of tolmetin sodium is in the peritoneum and that tolmetin sodium produces its anti-writhing action mainly by a peripheral mechanism in the rat [21].
• 3 When the rat was given tolmetin sodium 5 mg/kg orally, a relatively large quantity of tolmetin was found in the peritoneal exudate and there was a rough correlation between anti-writhing activity and the exudate tolmetin content [21].
• This normalization of T-cell function by tolmetin was associated with clinical improvement [22].

Associations of tolmetin with other chemical compounds

• Newer aspirin substitutes (mefenamic acid, fenoprofen, naproxen, tolmetin and ibuprofen) appear to cause less faecal blood loss than aspirin but their long-term effects have not been fully evaluated [23].
• 2 Tolmetin sodium was administered to the rat between 15 and 60 min after intraperitoneal injection of 1 ml of a 1% acetic acid aqueous solution [21].
• We conclude that tolmetin, naproxen, and ibuprofen can displace both carbamazepine and valproic acid from protein binding, but uremic serum contains an inhibitor that blocks valproic acid-naproxen interaction [24].
• QA (1 mM) induced lipid peroxidation in rat brain homogenate was significantly curtailed by co-treatment of the homogenate with tolmetin and/or sulindac [25].
• We have performed a single blind crossover study comparing naproxen 10 mg/kg/day, tolmetin 25 mg/kg/day and diclofenac 2 mg/kg/day in 28 children with seronegative JCA over 12 weeks [26].

Gene context of tolmetin

• 8. Cyclooxygenase inhibitors (0.001 to 10 mM) decreased sperm mobility: indomethacin 15 to 100%; diclofenac 4 to 100%; tolmetin 27 to 74%; aspirin (tested at 0.01 to 15 mM) 22 to 42%; resveratrol (COX-1) and NS-398 (COX-2), both tested at 0.1 to 10 mM, 38 to 98% and 44 to 85%, respectively [27].
• The aim of the study was to evaluate the toxicity of non-selective (tolmetin, ibuprofen and piroxicam) and selective (DFU) cyclooxygenase-2 inhibitors on pregnant and non-pregnant rats [28].
• With HPLC analysis, tolmetin, tolmetin glucuronide, and the isomers of tolmetin glucuronide, which result from intramolecular acyl migration in vivo, were detected in the plasma up to 4 hours after administration, whereas these conjugates were present in the urine up to 24 hours [16].
• The superiority of TGA relative to tolmetin sodium in alleviating this condition was demonstrated by inhibition of paw swelling and reduction of the degenerative bone changes that are associated with the progression of this chronic animal model of rheumatoid arthritis in humans [12].
• Clinical use of tolmetin sodium in patients with ankylosing spondylitis: a review [29].

Analytical, diagnostic and therapeutic context of tolmetin

• Six tolmetin-containing peptides (indicated by absorbance at 313 nm) were isolated by high-pressure liquid chromatography and analyzed by liquid secondary-ion mass spectrometry and collision-induced dissociation, using a four-sector tandem mass spectrometer [7].
• The pharmacokinetics of the new anti-inflammatory agent tolmetin have been studied after its oral administration to normal subjects and to patients with rheumatoid arthritis [30].
• The in vivo stability of tolmetin-plasma protein adducts was characterized in six healthy human volunteers after a 400 mg single dose and after a multiple-dose regimen of 400 mg tolmetin every 12 hours for 10 days [10].
• Serologic tests showed that in the absence of tolmetin, the patient had a negative antibody screening test but a strongly positive direct antiglobulin test [31].
• The double-blind study involved 14 patients (7 tolmetin sodium, 7 placebo), and the long-term study involved 24 patients [32].

References