EFFECTS OF INDOMETHACIN ON THE PHARMACOKINETICS AND PHARMACODYNAMICS OF PREDNISOLONE TN RATS

The effect of indomethacin on the disposition of prednisolone and the induction of tyrosine aminotransferase (TAT) was examined in male Spra gue-Dawley rats. Rats were pretreated with either indomethacin (5 mg/k g, intraperitoneally) or phosphate buffered saline (control) twice dai ly for 6 days followed by a single dose of prednisolone. Blood samples were collected after prednisolone administration. In separate animals , hepatic TAT activity (pharmacologic effect) was measured 4 h after t he prednisolone dose. In addition, the effect of indomethacin on the i n vitro protein binding of prednisolone was examined in pooled rat and human plasma. The clearance and apparent volume of distribution df pr ednisolone in the control and indomethacin-treated animals Were simila r, averaging 4.71 versus 4.05 L/h/kg and 1.37 versus 1.33 L/kg, respec tively. The elimination half-life was 0.48 h in both groups. Indometha cin also did not affect the protein binding of prednisolone in rat or human plasma. However, indomethacin pretreatment increased the hepatic TAT activity induced by prednisolone. These studies indicate that ind omethacin may affect the pharmacological effects of prednisolone witho ut influencing its pharmacokinetics.