Effects of proton pump inhibitors on thyroid hormone metabolism in rats: A comparison of UDP-glucuronyltransferase induction

Abstract

The effects of proton pump inhibitors on thyroid hormone metabolism in rats were examined. Pantoprazole, omeprazole, and lansoprazole were administered repeatedly to female SD rats at doses of 5, 50, and 300 mg/kg/day for 1 week, and changes in UDP-glucuronyltransferase activities were examined. Increases in o-aminophenol UDP-glucuronyltransferase activity, which was measured as that responsible for the glucuronidation of thyroxine, were evident following 7-day high-dose administration of all the proton pump inhibitors tested. Of the three proton pump inhibitors investigated, o-aminophenol UDP-glucuronyltransferase activity was greatest following the high-dose administration of omeprazole. Androsterone UDP-glucuronyltransferase activity in rats treated with the proton pump inhibitors increased significantly, but these increases were smaller than those of o-aminophenol UDP-glucuronyltransferase. Pantoprazole and omeprazole treatment did not affect plasma T 4 or T 3 significantly, whereas lansoprazole treatment produced marked reductions in plasma T 4 but did not affect plasma T 3 significantly. After administration of 125I-labeled thyroid hormone to rats treated with the proton pump inhibitors, biliary excretion of radioactivity increased significantly in omeprazole- and lansoprazoletreated rats; these increases were attributed to induction of liver thyroxine UDP-glucuronyltransferase activities. The order of biliary excretion of radioactivity, as well as the o-aminophenol UDP-glucuronyltransferase activity, in the treated animals was: omeprazole > lansoprazole > pantoprazole. Therefore, repeated administration of the proton pump inhibitors increased thyroxine-metabolizing activity via induction of UDP-glucuronyltransferase, and this induction by pantoprazole was less pronounced than that by omeprazole or lansoprazole.