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- W2059189302 abstract "Metoprolol is a selective β1-adrenergic receptor antagonist metabolized by hepatic cytochrome P450s (CYPs). In this study, we evaluated pharmacokinetic changes following intravenous (i.v.) and oral metoprolol in rats with diabetes mellitus induced by streptozotocin (DMIS). Metoprolol has an intermediate hepatic extraction ratio in rats (0.586–0.617), and it is assumed that the liver is exclusively responsible for metoprolol metabolism. Thus, the hepatic clearance, CLH (the non-renal clearance, CLNR) of metoprolol depends on the hepatic blood flow rate (QH), the free fraction in plasma (fp), and in vitro hepatic intrinsic clearance, CLint. After i.v. administration of 1.5 mg/kg metoprolol to DMIS rats, its CLNR was 40.9% faster than control animals. This could be due to a significantly faster QH because hepatic CLint and fp were comparable between the two groups of rats due to unchanged hepatic CYP2D activity. After oral administration of 1.5 mg/kg metoprolol to DMIS rats, gastrointestinal absorption was >99% of the oral dose for both groups, while the area under the curve (AUC) was 27.9% smaller, which could be caused by the greater hepatic metabolism seen in the i.v. study. These findings have potential therapeutic implications, assuming that the DMIS rats qualitatively reflect similar changes in patients with diabetes." @default.
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- W2059189302 date "2013-11-01" @default.
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- W2059189302 title "Faster non-renal clearance of metoprolol in streptozotocin-induced diabetes mellitus rats" @default.
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- W2059189302 doi "https://doi.org/10.1016/j.ejps.2013.08.022" @default.
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