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Metabolism and Excretion Rosiglitazone maleate Rosiglitazone is extensively metabolized with no unchanged drug excreted in the urine. The major routes of metabolism were N-demethylation and hydroxylation, followed by conjugation with sulfate and glucuronic acid. All the circulating metabolites are considerably less potent than parent and, therefore, are not expected to contribute to the insulin-sensitizing activity of rosiglitazone. Text Continues Below
In vitro data demonstrate that rosiglitazone is predominantly metabolized by cytochrome P450 (CYP) isoenzyme 2C8, with CYP2C9 contributing as a minor pathway. Following oral or intravenous administration of [ 14 C] rosiglitazone maleate, approximately 64% and 23% of the dose was eliminated in the urine and in the feces, respectively. The plasma half-life of [ 14 C] related material ranged from 103 to 158 hours. Metformin hydrochloride Intravenous single-dose studies in normal subjects demonstrate that metformin is excreted unchanged in the urine and does not undergo hepatic metabolism (no metabolites have been identified in humans) nor biliary excretion. Renal clearance approximately 3.5 times greater than creatinine clearance which indicates that tubular secretion is the major route of metformin elimination. Following oral administration, approximately 90% of the absorbed drug is eliminated via the renal route within the first 24 hours, with a plasma elimination half-life of approximately 6.2 hours. In blood, the elimination half-life is approximately 17.6 hours, suggesting that the erythrocyte mass may be a compartment of distribution. Special Populations Renal Impairment In subjects with decreased renal function (based on measured creatinine clearance), the plasma and blood half-life of metformin is prolonged and the renal clearance is decreased in proportion to the decrease in creatinine clearance (see WARNINGS, also see GLUCOPHAGE (r) prescribing information, and CLINICAL PHARMACOLOGY, Pharmacokinetics). Since metformin is contraindicated in patients with renal impairment, administration of AVANDAMET is contraindicated in these patients. Page: << Prev | 1 | 2 | 3 | 4 | 5 | Next >>
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