頁籤選單縮合
| 題 名 | Preparation and Intestinal Absorption of L-Dopa-D-phenylglycine=L-Dopa-D-phenylglycine之合成及小腸吸收 |
|---|---|
| 作 者 | 王惠珀; 范揚彬; 盧曉華; 徐文俐; | 書刊名 | 藥物食品分析 |
| 卷 期 | 10:2 2002.06[民91.06] |
| 頁 次 | 頁81-87 |
| 分類號 | 418.1 |
| 關鍵詞 | 雙胜冴前驅藥; 小腸小胜冴運輸體; L-Dopa-D-phenylglycine; Dipeptide mimetics; PepT1; Intestinal absorption; |
| 語 文 | 英文(English) |
| 中文摘要 | 本研究合成雙胜肽L-dopa-D-phenylglycine,作為 dopamine之前驅藥。設計原理為以D-phenylglycine作為藥引子,導引子,導引L-dopa透過小腸小胜肽運輸體(oligopeptide transporter, PepT1)吸收。我們由大鼠小腸黏膜製作刷狀緣膜包囊(brush border membrane vesicle, BBMV),藉由L-dopa-D-phenylglycine與L-Gly-L-Pro, LGly-L-Phe及cephradine對PepT1的競爭,測量其 BBMV 之吸收量,探討L-dopa-D-phenylglycine是否透過腸小胜肽運輸體吸收。在雙胜肽L-Gly-L-Pro, L-Gly-L-Phe及擬三胜肽cephradine的存在下,L-dopa-Dphenylglycine在BBMV之吸收分別降為54.1±4.5%, 57.6±5.2%及62.9±10.2%,胺基酸L-Phe則不影響其吸收,顯示L-dopa-D-phenylglycine可透過小腸小胜肽運輸體吸收。在活體Wistar大鼠進行空腸灌流試驗達到血中濃度恆定時,L-dopa-D-phenylglycine的血中濃度(104.0±12.9 μg/mL)以當量數計為L-dopa血中濃度 (1.24 μg/mL)的50.1倍,顯示L-dopa-D-Phenylglycine在大鼠小腸具有優於L-dopa的吸收。這個雙胜肽前驅藥在大鼠的吸收動力學研究證明D-Phenylglycine具有藥引子功能,可促進L-dopa藉由小腸PepT1吸收。 |
| 英文摘要 | L-Dopa-D-phenylglycine was synthesized in this laboratory as L-dopa derivative for improving its intestinal absorption. As designed for transport through the intestine via oligopeptide transporter (PepT1), the competition of this dipeptide with known substrates for PepT1 in brush-border membrane vesicle (BBMV) was investigated. At the presence of L-Glycinyl-L-proline (L-Gly-L-Pro), L-Glycinyl-Lphenylalanine (L-Gly-L-Phe) or cephradine, the uptake of L-dopa-D-phenylglycine in BBMV was reduced to 54.1 ± 4.5%, 57.6 ± 5.2% or 62.9 ± 10.2%, respectively. The inhibition by these dipeptides and the tripeptide mimetic amino--lactam was significantly higher than by amino acids L-Phenylalanine (L-Phe) or L-dopa. The results suggested that the intestinal H+-coupled PepT1 was involved in the uptake of L-dopa-D-phenylglycine. The steady state plasma concentrations of L-dopa-D-phenylglycine and L-dopa in rats after a single pass in-situ jejunal perfusion with 0.1 mM perfusate were 104.0 ± 12.90 μg/mL and 1.24 μg/mL respectively. L-Dopa-D-phenylglycine demonstrated a 50.1 fold higher plasma concentration, in terms of molar ratio, than that of L-dopa. D-Phenylglycine was proved to be a satisfactory moiety for the improvement of L-dopa absorption in the intestine. |
本系統中英文摘要資訊取自各篇刊載內容。