New Findings from Discovery Research Center Describe Advances in Sulfonylurea Compounds (Pharmacokinetics of tolbutamide and its metabolite 4-hydroxy tolbutamide in poloxamer 407-induced hyperlipidemic rats)
By a News Reporter-Staff News Editor at Biotech Week -- Data detailed on Sulfonylurea Compounds have been presented. According to news reporting originating from Suwon, South Korea, by NewsRx correspondents, research stated, "Under hyperlipidemic conditions, there are likely to be alterations in the pharmacokinetics of CYP2C11 substrates following decreased expression of CYP2C11, which is homologous to human CYP2C9. The pharmacokinetics of tolbutamide (TB) and its metabolite 4-hydroxy tolbutamide (4-OHTB) were evaluated as a CYP2C11 probe after intravenous and oral administration of 10 mg/kg tolbutamide to poloxamer 407-induced hyperlipidemic rats (HL rats)."
Our news editors obtained a quote from the research from Discovery Research Center, "Changes in the expression and metabolic activity of hepatic CYP2C11 and the plasma protein binding of tolbutamide in HL rats were also evaluated. The total area under the plasma concentration-time curve (AUC) of tolbutamide in HL rats after intravenous administration was comparable to that in controls due to their comparable non-renal clearance (CLNR). The free fractions of tolbutamide in plasma were comparable between the control and HL rats. The 4-hydroxylated metabolite formation ratio (AUC(4-OHTB)/AUC(TB)) in HL rats was significantly smaller than that in the control rats as a result of the reduced expression of hepatic CYP2C11 (by 15.0%) and decreased hepatic CLint (by 28.8%) for metabolism of tolbutamide to 4-OHTB via CYP2C11. Similar pharmacokinetic changes were observed in HL rats after oral administration of tolbutamide. These findings have potential therapeutic implications, assuming that the HL rat model qualitatively reflects similar changes in patients with hyperlipidemia."
According to the news editors, the research concluded: "Since other sulfonylureas in clinical use are substrates of CYP2C9, their hepatic CLint changes have the potential to cause clinically relevant pharmacokinetic changes in a hyperlipidemic state."
For more information on this research see: Pharmacokinetics of tolbutamide and its metabolite 4-hydroxy tolbutamide in poloxamer 407-induced hyperlipidemic rats. Biopharmaceutics & Drug Disposition, 2014;35(5):264-274. Biopharmaceutics & Drug Disposition can be contacted at: Wiley-Blackwell, 111 River St, Hoboken 07030-5774, NJ, USA. (Wiley-Blackwell - www.wiley.com/; Biopharmaceutics & Drug Disposition - onlinelibrary.wiley.com/journal/10.1002/(ISSN)1099-081X)
The news editors report that additional information may be obtained by contacting M.R. Choi, C&C Res Labs, Discovery Res Center, Suwon, South Korea. Additional authors for this research include M.H. Kwon, Y.Y. Cho, H.D. Choi, Y.C. Kim and H.E. Kang (see also Sulfonylurea Compounds).
Keywords for this news article include: Asia, Pharmaceuticals, Suwon, Drugs, Therapy, South Korea, Tolbutamide, Pharmacokinetics, Sulfonylurea Compounds
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