| 体内研究 | 在体内,西格列汀磷酸盐抑制血浆DPP-4活性的ED50值在给药后7小时和自由喂养的Han-Wistar大鼠中给药后24小时30mg/kg时计算为2.3mg/kg [1]。链脲佐菌素诱导的1型糖尿病小鼠模型在血浆中表现出升高的DPP-4水平,其在西格列汀磷酸盐饮食中可在小鼠中基本上被抑制。这是通过对高血糖的调节产生积极影响来实现的,可能通过延长胰岛移植物的存活率[4]。 Sitagliptin phosphate的血浆清除率和分布容量在大鼠(40-48 mL/min/kg,7-9 L/kg)中高于狗(9 mL/min/kg,3 L/kg);大鼠的半衰期较短,2小时与狗的4小时相比[5]。 |
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| 参考文献 | [1]. Thomas, L., et al. (R)-8-(3-amino-piperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylm ethyl)-3,7-dihydro-purine-2,6-dione (BI 1356), a novel xanthine-based dipeptidyl peptidase 4 inhibitor, has a superior potency and longer duration of acti [2]. Kim, S.J., et al., Dipeptidyl peptidase IV inhibition with MK0431 improves islet graft survival in diabetic NOD mice partially via T-cell modulation. Diabetes, 2009. 58(3): p. 641-51. [3]. Sangle, G.V., et al., Novel biological action of the dipeptidylpeptidase-IV inhibitor, sitagliptin, as a glucagon-like peptide-1 secretagogue. Endocrinology, 2012. 153(2): p. 564-73. [4]. Kim, S.J., et al., Inhibition of dipeptidyl peptidase IV with sitagliptin (MK0431) prolongs islet graft survival in streptozotocin-induced diabetic mice. Diabetes, 2008. 57(5): p. 1331-9. [5]. Beconi, M.G., et al. Disposition of the dipeptidyl peptidase 4 inhibitor sitagliptin in rats and dogs. Drug Metab Dispos, 2007. 35(4): p. 525-32. |
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