| 體內(nèi)研究 | 在體內(nèi),西格列汀磷酸鹽抑制血漿DPP-4活性的ED50值在給藥后7小時(shí)和自由喂養(yǎng)的Han-Wistar大鼠中給藥后24小時(shí)30mg/kg時(shí)計(jì)算為2.3mg/kg [1]。鏈脲佐菌素誘導(dǎo)的1型糖尿病小鼠模型在血漿中表現(xiàn)出升高的DPP-4水平,其在西格列汀磷酸鹽飲食中可在小鼠中基本上被抑制。這是通過對(duì)高血糖的調(diào)節(jié)產(chǎn)生積極影響來實(shí)現(xiàn)的,可能通過延長胰島移植物的存活率[4]。 Sitagliptin phosphate的血漿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);大鼠的半衰期較短,2小時(shí)與狗的4小時(shí)相比[5]。 |
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| 參考文獻(xiàn) | [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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