Disease relevance of C12583

• Tolfenamic acid is as effective as ergotamine during migraine attacks [1].
• Prolonged treatment with tolfenamic acid in inflammatory rheumatic diseases [2].
• There seems no reason to reduce the dose of tolfenamic acid in patients with compensated alcoholic cirrhosis [3].
• PROCEDURE: Blood samples were collected at 0, 5, 10, 15, 30, 45, and 60 minutes and at 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 13, 14, 15, and 16 hours after IV administration of tolfenamic acid (2.0 mg/kg of body weight) [4].
• The absence of gastritis in each subject during treatment with tolfenamic acid was confirmed both gastroscopically and histologically [5].

High impact information on C12583

• The synthesis of prostaglandins and (11R)-hydroxyeicosatetraenoic acid was inhibited by mammalian cyclooxygenase inhibitors (indomethacin, aspirin, and tolfenamic acid), while the formation of the products of the 8-lipoxygenase/allene oxide pathway was not affected or was increased [6].
• The role of the migrating motor complex (MMC) of the small intestine in the absorption of an enterally administered marker (tolfenamic acid, TA) used to investigate enterohepatic recycling was studied in the fasted dog [7].
• Tolfenamic acid (TA), a potent inhibitor of prostaglandin (PG) biosynthesis and action, was tested prophylactically against hangover symptoms in 30 healthy volunteers in a double-blind cross-over study [8].
• A multi-residue liquid chromatography/tandem mass spectrometry method (LC/MS2) was developed for the detection of the non-steroidal anti-inflammatory drugs acetylsalicylic acid (via the marker residue salicylic acid), flunixin, phenylbutazone, tolfenamic acid, meloxicam and ketoprofen, in bovine muscle [9].
• The mean recoveries from serum samples spiked with furosemide (5.0 x 10(-7), 2.0 x 10(-6) and 8.0 x 10(-6) mol l-1), mefenamic acid (3.0 x 10(-6), 9.0 x 10(-6) and 3.0 x 10(-5) mol l-1) and tolfenamic acid (3.1 x 10(-6), 12.5 x 10(-6) and 2.5 x 10(-5) mol l-1) were 96 +/- 8, 101 +/- 5 and 98 +/- 7%, respectively [10].

Chemical compound and disease context of C12583

• When the patients were studied without migraine the serum concentrations of tolfenamic acid 45 min and 60 min after its administration were higher after metoclopramide than after placebo pretreatment [11].
• In this study, tolfenamic acid and oral sumatriptan are comparably effective in the acute treatment of migraine [12].
• Prophylactic treatment of migraine with tolfenamic acid, propranolol and placebo [13].
• In a double-blind cross-over study we compared tolfenamic acid with paracetamol in out-patients with common migraine (migraine without aura) [14].
• If the patient has some degree of renal insufficiency, try to select drugs that are hepatically metabolized and excreted in bile rather than eliminated by the kidneys (eg, doxycycline, tolfenamic acid) [15].

Biological context of C12583

• Tolfenamic acid displayed linear pharmacokinetics since the area under the plasma concentration time curve (AUC) values were 13.74 +/- 1.88, 29.82 +/- 6.53 and 50.52 +/- 5.73 micrograms/ml.h following administration of 2, 4 and 8 mg/kg, respectively [16].
• Tolfenamic acid significantly reduced the elevated skin temperature over carrageenan administered cages at all dose levels [16].
• Tolfenamic acid proved to be a potent inhibitor of ex vivo thromboxane B2 generation in clotting blood [16].
• IC50 values were 0.64 muM for tolfenamic acid, 0.76 muM for indomethacin, and 7 mM for acetylsalicylic acid [17].
• Protein binding of tolfenamic acid in the plasma from patients with renal and hepatic disease [18].

Anatomical context of C12583

• The present work was designed to study the pharmacological control of the receptor-mediated activation of human neutrophils by tolfenamic acid (2(-)[(3-chloro-2-methylphenyl)-amino]benzoic acid) [19].
• Tolfenamic acid did not significantly alter 12-HETE generation or white blood cell accumulation in inflammatory exudate [16].
• Tolfenamic acid was administered to beagle dogs at 2, 4 and 8 mg/kg bodyweight i.m. and the concentration of drug in plasma and in inflamed (administered carrageenan) and non-inflamed subcutaneous tissue cage fluid was measured [16].
• The findings of this study are comparable to those of other studies and it is concluded that tolfenamic acid, in the relatively high dosage employed in this trial, is free from any irritant effect on the gastric mucosa [5].
• Comparison of in vitro effects of flunixin and tolfenamic acid on human leukocyte and platelet functions [20].

Associations of C12583 with other chemical compounds

• Protein kinase C activity in sonicated human neutrophils and the purified enzyme from rat brain were inhibited by the protein kinase inhibitor H-7 (1-(5-isoquinolinylsulfonyl)-2-methylpiperazine) but not by tolfenamic acid [19].
• At drug concentrations causing a significant suppression of O2- generation, diclofenac showed a slight and tolfenamic acid a marked inhibition of [3H]FMLP binding to its cellular receptor; indomethacin has earlier been shown to inhibit FMLP-binding slightly [21].
• The measurements of binding properties in whole blood and blood cell--buffer suspension showed that tolfenamic acid interacts with the lipid membrane structures of blood cells, while salicylic acid is distributed into the aqueous cell space [18].
• Meloxicam and tolfenamic acid were selective for COX-2 [22].
• Values of 71.6, 49.0, and 50.8 kcal/mol are obtained respectively for (1) the polymorph I to II transition of mefenamic acid, (2) the polymorph I to II transition of tolfenamic acid, and (3) the polymorph III to I transition of flufenamic acid [23].

Gene context of C12583

• CONCLUSIONS AND CLINICAL RELEVANCE: Canine COX-2 was selectively inhibited by etodolac, nimesulide, and NS398; tolfenamic acid and carprofen also appeared to be preferential COX-2 inhibitors in dogs [24].
• RESULTS: Tolfenamic acid and structurally related biaryl derivatives induced degradation of Sp1, Sp3, and Sp4 in pancreatic cancer cells [25].
• Nimesulide had the next highest selectivity for COX2 (38-fold), and tolfenamic acid and meclofenamic acid had 15-fold selectivity for COX2 [26].
• For example, tumors from mice treated with tolfenamic acid (50 mg/kg) had statistically significantly lower VEGF levels (45%, 95% confidence interval = 39% to 51%; P = .009) than tumors from control mice [25].
• Tolfenamic acid inhibited also FMLP-induced chemotaxis at the same concentration range (IC50 46 microM) [27].

Analytical, diagnostic and therapeutic context of C12583

• The efficacy of an anti-prostaglandin, tolfenamic acid (T.A.), in the prevention of side-effects after insertion of a copper-T200 intrauterine contraceptive device (I.U.D.) was evaluated in a double-blind trial in 160 women [28].
• In this study, the metabolites of tolfenamic acid were identified by 1H nuclear magnetic resonance (NMR) spectroscopy in urine samples obtained on days 7 to 10 from a human volunteer after oral administration of 200 mg of the drug three times per day (steady-state plasma concentration) [29].
• An HPLC method was developed that simultaneously separates all the phase II metabolites identified as well as some phase I metabolites in urine samples obtained after intake of tolfenamic acid [29].
• Tolfenamic acid and its metabolites were separated by TLC and were quantitated by liquid scintillation counting [30].
• Comparative effects of tolfenamic acid and acetylsalicylic acid on human gastric mucosa. A double-blind crossover trial employing gastroscopy, extern gastrocamera and multiple biopsies [5].

References