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Distribution Budesonide has a volume of distribution of approximately 2-3 L/ kg. The volume of distribution for the 22R epimer is almost twice that of the 22S epimer. Protein binding of budesonide in vitro is constant (85Ð 90%) over a concentration range (1-100 nmol/ L) which exceeded that achieved after administration of recommended doses. Budesonide shows little to no binding to glucocorticosteroid binding globulin. It rapidly equilibrates with red blood cells in a concentration independent manner with a blood/ plasma ratio of about 0.8. Metabolism Text Continues Below
Budesonide is rapidly and extensively metabolized in humans by the liver. Two major metabolites (16 -hydroxyprednisolone and 6ß-hydroxybudes-onide) are formed via cytochrome P450 3A isoenzyme-catalyzed biotransformation. Known metabolic inhibitors of cytochrome P450 3A (eg, ketoconazole), or significant hepatic impairment, may increase the systemic exposure of unmetabolized budesonide (see WARNINGS and PRECAUTIONS). In vitro studies on the binding of the two primary metabolites to the glucocorticoid receptor indicate that they have less than 1% of the affinity for the receptor as the parent compound budesonide. In vitro studies have evaluated sites of metabolism and showed negligible metabolism in skin, lung, and serum. No qualitative difference between the in vitro and in vivo metabolic patterns could be detected. Elimination Budesonide is excreted in the urine and feces in the form of metabolites. After intranasal administration of a radiolabeled dose, 2/ 3 of the radioac-tivity was found in the urine and the remainder in the feces. The main metabolites of budesonide in the 0-24 hour urine sample following IV administration are 16 -hydroxyprednisolone (24%) and 6ß-hydroxy-budesonide (5%). An additional 34% of the radioactivity recovered in the urine was identified as conjugates. Page: << Prev | 1 | 2 | 3 | 4 | 5 | Next >>
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