EFFECTS OF PROTON PUMP INHIBITORS ON THYROID-HORMONE METABOLISM IN RATS - A COMPARISON OF UDP-GLUCURONOSYLTRANSFERASE INDUCTION

The effects of proton pump inhibitors on thyroid hormone metabolism in rats were examined. Pantoprazole, omeprazole, and lansoprazole were a dministered repeatedly to female SD rats at doses of 5, 50, and 300 mg /kg/day for 1 week, and changes in UDP-glucuronyltransferase activitie s were examined. Increases in o-aminophenol UDP-glucuronyltransferase activity, which was measured as that responsible for the glucuronidati on of thyroxine, were evident following 7-day high-dose administration of all the proton pump inhibitors tested. Of the three proton pump in hibitors investigated, o-aminophenol UDP-glucuronyltransferase activit y was est following the high-dose administration of omeprazole. Andros terone UDP-glucuronyltransferase activity in rats treated with the pro ton pump inhibitors increased significantly, but these increases were smaller than those of o-aminophenol UDP-glucuronyltransferase. Pantopr azole and omeprazole treatment did not affect plasma T-4 or T-3 signif icantly, whereas lansoprazole treatment produced marked reductions in plasma T-4 but did not affect plasma T-3 significantly. After administ ration of I-125-labeled thyroid hormone to rats treated with the proto n pump inhibitors, biliary excretion of radioactivity increased signif icantly in omeprazole-and lansoprazole-treated rats; these increases w ere attributed to induction of liver thyroxine UDP-glucuronyltransfera se activities. The order of biliary excretion of radioactivity, as wel l as the o-aminophenol UDP-glucuronyltransferase activity, in the trea ted animals was: omeprazole > lansoprazole > pantoprazole. Therefore, repeated administration of the proton pump inhibitors increased thyrox ine-metabolizing activity via induction of UDP-glucuronyltransferase, and this induction by pantoprazole was less pronounced than that by om eprazole or lansoprazole. (C) 1997 Elsevier Science Inc.