[Indomethacin kinetics and urinary excretion of prostaglandin E2 following oral administration of various dosage forms of indomethacin].
In a controlled crossover study healthy volunteers received a single oral dose of 75 mg indomethacin, 75 mg sustained-release indomethacin, or the new therapeutic system indomethacin Gits 7/85. Dependence on the time of administration was investigated by comparing the plasma level curves obtained following morning and evening administration of indomethacin and indomethacin Gits. Blood samples were taken at defined intervals following administration for determination of indomethacin plasma levels. To determine urinary excretion of prostaglandin (PG)E2, urine was collected during four consecutive 6 h-clearance periods after administration of the indomethacin preparations. The plasma level curve following administration of indomethacin Gits 7/85 did not exhibit clearly distinct initial peaks and, in contrast to the other drug preparations, remained nearly constant over 10-12 h. Indomethacin induced a significant suppression of urinary PGE2 excretion over a period of 12 h, whereas both sustained release indomethacin and indomethacin Gits 7/85 decreased urinary PGE2 excretion for 18 h. Neither the plasma concentration curve of indomethacin nor the inhibitory effect on urinary PGE2 excretion was dependent on the time of administration. Initial central nervous side effects, such as dizziness, were reported by all volunteers after taking indomethacin and by half of the volunteers following sustained release indomethacin, whereas no adverse effects were observed after administration of indomethacin Gits 7/85. The present study demonstrates that indomethacin Gits 7/85 produces no initial peaks of plasma levels but rather a sustained concentration plateau. The excellent tolerability of indomethacin Gits 7/85 is probably due to the lack of peak plasma concentrations.