STUDIES ON THE ABSORPTION, DISTRIBUTION AND EXCRETION OF INDOMETHACIN IN VARIOUS SPECIES

Indomethacin is promptly and completely absorbed after oral administration. The half-life of the drug in plasma varies among species, ranging from 20 min to 4 hr. Most of the dose is eliminated from the body in 24 hr, the route of excretion varying among species. The drug is extensively excreted in the bile, largely reabsorbed and excreted in the urine in most species except the dog, in which reabsorption of biliary material does not result in eventual urinary excretion of the drug. Only minimal amounts of free drug are found in the urine. No evidence was obtained for accumulation of the drug in man. Little passage into cerebrospinal fluid takes place. Indomethacin is concentrated in various tissues of the guinea pig, but not of the rat. The drug is highly bound to plasma protein. No evidence for accumulation of the drug in the intestinal wall of either rats or guinea pigs was seen. The dog was shown to convert indomethacin to indomethacin glucuronide, which is excreted in the bile.