伊曲康唑对盐酸非索非那定的药代学和药效学的影响与凋亡基因多态性。
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铁城JH,尹年,香港WS,阮点,李党卫军,崔YG, Cha IJ, Shin詹
伊曲康唑对盐酸非索非那定的药代学和药效学的影响与凋亡基因多态性。
中国新药杂志。2005年8月,78 (2):191 - 201。
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16084853 (在PubMed]
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目的:我们的目的是评价伊曲康唑的影响,22抑制剂,盐酸非索非那定的药代学和药效学,22衬底,在关系的多药耐药性1基因(凋亡)G2677T / C3435T单体型。方法:单剂量口服180毫克盐酸非索非那定的管理与2677 gg / 7健康受试者3435 cc (G / C)单体型和7 2677 tt / 3435 tt (T / T)单体型。1小时前的盐酸非索非那定剂量,伊曲康唑200毫克或安慰剂管理受试者在一个双盲,随机,交叉方式与洗脱期2周。Histamine-induced水疱和耀斑反应测定评估抗组胺剂反应的影响。结果:在安慰剂阶段,盐酸非索非那定的药代动力学参数无显著区别2凋亡单;从时间0到正无穷曲线下的面积(AUC (0-infinity))的盐酸非索非那定T / T和G / C组是5194.0 + / - 1910.8和4040.4 + / - 1832.2 ng.mL (1) . h(1),分别(P = .271),和口述间隙(CL / F)是530.9 + / - 191.1和806.0 + / - 355.3 mL.h (1) .kg(1),分别(P = .096)。伊曲康唑的性格,22的衬底,不是2个单之间的明显不同。然而,伊曲康唑预处理后的盐酸非索非那定的差异药物动力学成为统计学意义;盐酸非索非那定AUC均值(0-infinity) T / T组明显高于G / C组(15630。6 + / - 5070.0和9252.9 + / - 2044.1 ng / mL。分别为h;P = .007)和CL / F T / T的科目低于G / C对象(167.0 + / - 33.3和292.3 + / - 42.2 mL.h (1) .kg(1),分别; P < .001). Itraconazole pretreatment caused more than a 3-fold increase in the peak concentration of fexofenadine and the area under the curve to 6 hours compared with the placebo phase. This resulted in a significantly higher suppression of the histamine-induced wheal and flare reactions in the itraconazole pretreatment phase compared with those in the placebo phase. CONCLUSION: The effect of MDR1 G2677T/C3435T haplotypes on fexofenadine disposition are magnified in the presence of itraconazole. Itraconazole pretreatment significantly altered the disposition of fexofenadine and thus its peripheral antihistamine effects.