Effect of tolmetin on renal function and prostaglandin metabolism

The effect of tolmetin on prostaglandin synthesis by minces of rat renal medulla and on prostaglandin cyclooxygenase of rabbit renal medulla was determined in vitro. The effect of tolmetin was compared to the effects of indomethacin and ibuprofen. Pretreatment of rats in vivo with tolmetin, indmethacin or ibuprofen reduced prostaglandin synthesis by minces of renal medulla. Incubation of medullary tissue in medium containing tolmetin or indomethacin also decreased prostaglandin production. Both drugs reduced O2 consumption by prostaglandin cyclooxygenase from rabbit renal medulla. In addition, the effect of tolmetin, indomethacin and ibuprofen on renal blood flow and the intrarenal distribution of renal blood flow was measured in anesthetized dogs. Tolmetin and ibuprofen resemble indomethacin in reducing renal blood flow and in shifting the distribution of renal cortical flow from the inner cortex toward the outer cortex. It is concluded that tolmetin is an effective inhibitor of prostaglandin synthesis and affects renal function in a fashion similar to other prostaglandin synthesis inhibitors.