salicylates and tolfenamic-acid

Topics: Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Ergotamine; Humans; Ibuprofen; Indoles; Migraine Disorders; Naproxen; ortho-Aminobenzoates; Oxazolidinones; Piperidines; Pyrrolidines; Salicylates; Sumatriptan; Triazoles; Tryptamines

Topics: Acute Disease; Adult; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Child; Diclofenac; Drug Therapy, Combination; Ergotamine; Humans; Ibuprofen; Indoles; Migraine Disorders; Naproxen; ortho-Aminobenzoates; Oxazolidinones; Piperidines; Pyrrolidines; Salicylates; Serotonin Receptor Agonists; Sumatriptan; Triazoles; Tryptamines

Environmental pH is important for the adsorption capacity of activated charcoal: in our experiments the unadsorbed fractions of aspirin and disopyramide were increased by 10-20-fold as the pH was altered from 1.2 to 7.0 or vice versa. In order to study the effect of pH in vivo, six subjects were given 500 mg aspirin, 200 mg disopyramide and 200 mg tolfenamic acid on an empty stomach with 20 ml of 8.5% magnesium hydroxide or without it. A small dose of charcoal, 2.5 g, administered immediately after the drugs, reduced the absorption of aspirin by 30-40%, whereas the absorption of disopyramide and tolfenamic acid was reduced by 70-80%. The inhibition of absorption was irrespective of whether the drugs were taken with the antacid or without it. Thus, in vivo other factors than the gastric pH must be more important in controlling the adsorption to activated charcoal. Accordingly, the simultaneous administration of antacids cannot be recommended to enhance the adsorptive capacity of charcoal in humans.

Topics: Absorption; Adult; Antidotes; Aspirin; Charcoal; Disopyramide; Female; Gastric Acid; Gastric Acidity Determination; Humans; Magnesium Hydroxide; Male; Middle Aged; ortho-Aminobenzoates; Salicylates; Salicylic Acid

The protein binding of tolfenamic acid in plasma from patients with renal and hepatic disorders was studied by equilibrium dialysis. Drug binding to the cellular components of whole blood and blood cell suspensions was also measured. Salicylic acid was used as the reference drug in all experiments. Renal and hepatic diseases increased the unbound fraction of tolfenamic acid. Free drug fractions were significantly correlated with changes in creatinine, urea, and total bilirubin, but not with those in albumin or total protein in plasma. Comparison of the theoretical binding parameters in control plasma and similar changes in protein binding in all the plasma samples studied revealed that tolfenamic acid and salicylic acid probably share a common primary binding site. The significance of the correlation permits use of salicylic acid as a model drug for predicting changes in the protein binding of tolfenamic acid. 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.

Topics: Adult; Aged; Erythrocytes; Female; Humans; Kidney Diseases; Liver Diseases; Male; Middle Aged; ortho-Aminobenzoates; Protein Binding; Salicylates; Salicylic Acid