临床药理学-综合案例分析.pdfVIP

药物相互作用及其临床意义 Drug-drug Interaction, DDI 毕惠嫦 中山大学药学院药物代谢与药动学实验室 药动学方面的相互作用 先用、后用或同时并用一种物质致使另一种药物在体 内吸收、分布、代谢、排泄等过程发生改变，从而 影响此药物的生物利用度。 A 吸收 D M 分布 代谢 E 排泄 诱导作用：应用某些药物后使肝药酶的浓度和活性增 加，从而使某些药物的代谢加速。 诱导剂通常对特定的CYP酶有专属性。 诱导作用的起始时间由药物的t1/2决定。 诱导作用的最大效应在用药1-2周后出现，停药后可能维持 数天乃至数周。 当诱导药物被清除和肝酶作用改变时，诱导作用即可逆转。 诱导结果：缩短药物的半衰期，加速药物的灭活、血药浓度 下降或代谢产物增加。 St. John’s Wort  54 Cases of 180 Cases Preliminary data suggest that St John’s wort induces the 3A4 isoform of the cytochrome P450 (CYP) enzyme system. Comedication with hypericum extract was recently shown to drastically reduce plasma concentration of cyclosporin, digoxin, and indinavir. 例如 Lancet 2000;355:547-548 St. John’s Wort Drug Metab Rev.2003;35(1):35-98 Fig 3. Induction of CYP3A4 and 2B6 by hyperforin of St. John’s wort through pregnane X receptor (PXR) activation. The binding of hyperforin to PXR produced a complex which was consequently bound by pregnane response element (PRE), leading to the expression of CYP3A4 and 2B6 and P-glycoprotein (PgP). 抑制作用：某些药物抑制肝药酶活性，使一些经 肝药酶代谢的药物灭活受阻，其药物作用加强。 • 应监测病人的血药浓度或调整用药剂量，以减少其 潜在毒性。 • 抑制剂在肝脏中达到足够浓度就可发生抑制作用， 并在24小时内达到最大。 • 一旦停用，逆转比诱导迅速。 Grapefruit juice  Containing various furanocoumarin derivatives that inhibit CYP3A4 located in the GI tract walls.  Concomitant use of GFJ is known to increase plasma concentrations of some dihydropyridine calcium antagonists, anti-allergic agents, immunosuppressive agents, and anti-HIV agents.  Hence since GFJ is a commonly used beverage, i