Tolmetin uptake into inflamed tissue in the rat

Concentrations of the antiinflammatory agent tolmetin have been measured by HPLC in inflamed and non-inflamed rat tissues after oral administration of tolmetin sodium dihydrate in solution (100 mg free acid/kg) and after topical administration of tolmetin (Tolectin gel, 1 g of a 5% gel, 250 mg free acid/kg). After oral administration of tolmetin, there was marked localisation of the drug in inflamed rat paws. Concentrations of tolmetin were significantly greater in inflamed paws than those in non-inflamed paws at each time studied (e.g. at 3 h after dosing, inflamed paw 30.5 micrograms/g, non-inflamed paw 14.9 micrograms/g). After a single topical application of tolmetin gel to the shaved backs of rats, tolmetin was well absorbed percutaneously into the non-inflamed dorsal muscle. After repeated topical application of tolmetin gel to the shaved backs of rats, daily for 4 consecutive days, concentrations of tolmetin (total micrograms/paw) similar in inflamed paws and in non-inflamed paws. After topical administration of tolmetin gel to rat paws, tolmetin was transported from treated paws to untreated paws, e.g. from non-inflamed paws to inflamed paws and vice versa. These studies showed that tolmetin applied topically reaches inflamed tissues in concentrations that exceed those in plasma.