...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The Journal of Clinical Pharmacology: Official Journal of the American College of Clinical Pharmacology >CYP2D6 inhibition by fluoxetine, paroxetine, sertraline, and venlafaxine in a crossover study: intraindividual variability and plasma concentration correlations.
【24h】

CYP2D6 inhibition by fluoxetine, paroxetine, sertraline, and venlafaxine in a crossover study: intraindividual variability and plasma concentration correlations.

机译：在一项交叉研究中，氟西汀，帕罗西汀，舍曲林和文拉法辛对CYP2D6的抑制作用：个体差异和血浆浓度相关性。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The authors report the CYP2D6 inhibitory effects of fluoxetine, paroxetine, sertraline, and venlafaxine in an open-label, multiple-dose, crossover design. Twelve CYP2D6 extensive metabolizers were phenotyped, using the dextromethorphan/dextrorphan (DM/DX) urinary ratio, before and after administration of fluoxetine 60 mg (loading dose strategy), paroxetine 20 mg, sertraline 100 mg, and venlafaxine 150 mg. Paroxetine, sertraline, and venlafaxine sequences were randomized with 2-week washouts between treatments; fluoxetine was the last antidepressant (AD) administered. Comparing within groups, baseline DM/DX ratios (0.017) were significantly lower than DM/DX ratios after treatment (DM/DXAD) with fluoxetine (0.313, p < 0.0001) and paroxetine (0.601, p < 0.0001) but not for sertraline (0.026, p = 0.066) or venlafaxine (0.023, p = 0.485). Between groups, DM/DXAD ratios were significantly higher for fluoxetine and paroxetine compared to sertraline and venlafaxine. No differences between DM/DXAD ratios were found for fluoxetine and paroxetine although more subjects phenocopied to PM status after receiving the latter (42% vs. 83%; chi 2 = 4.44, p = 0.049, df = 1). Similarly, no differences between DM/DXAD ratios were found for sertraline and venlafaxine. Of note, the DM/DXAD for 1 subject was much lower after treatment with paroxetine (0.058) compared to fluoxetine (0.490), while another subject exhibited a much lower ratio after treatment with fluoxetine (0.095) compared to paroxetine (0.397). Significant correlations between AD plasma concentration and DM/DXAD were found for paroxetine (r2 = 0.404, p = 0.026) and sertraline (r2 = 0.64, p = 0.002) but not fluoxetine or venlafaxine. In addition, DM/DXAD correlated with baseline isoenzyme activity for paroxetine, sertraline, and venlafaxine groups. These results demonstrate the potent, but variable, CYP2D6 inhibition of fluoxetine and paroxetine compared to sertraline and venlafaxine. CYP2D6 inhibition may be related, in part, to dose, plasma concentration, and baseline isoenzyme activity, and these correlations merit further investigation.
机译：作者报告了在开放标签，多剂量，交叉设计中氟西汀，帕罗西汀，舍曲林和文拉法辛对CYP2D6的抑制作用。在使用氟西汀60 mg（负荷剂量策略），帕罗西汀20 mg，舍曲林100 mg和文拉法辛150 mg给药前后，使用右美沙芬/右美沙芬（DM / DX）尿比对十二种CYP2D6广泛代谢者进行表型分析。帕罗西汀，舍曲林和文拉法辛序列在治疗之间进行为期2周的洗脱，随机分组。氟西汀是最后使用的抗抑郁药（AD）。在各组之间进行比较，氟西汀（0.313，p <0.0001）和帕罗西汀（0.601，p <0.0001）治疗后的DM / DX基线比率（0.017）显着低于DM / DXAD（DM / DXAD），但舍曲林（ 0.026，p = 0.066）或文拉法辛（0.023，p = 0.485）。在各组之间，与舍曲林和文拉法辛相比，氟西汀和帕罗西汀的DM / DXAD比明显更高。氟西汀和帕罗西汀的DM / DXAD比之间没有差异，尽管更多的受试者在接受后者后表型呈PM状态（42％vs. 83％; chi 2 = 4.44，p = 0.049，df = 1）。同样，舍曲林和文拉法辛的DM / DXAD比值之间也没有差异。值得注意的是，与氟西汀（0.490）相比，帕罗西汀（0.058）治疗后1名受试者的DM / DXAD低得多，而与帕罗西汀（0.397）相比，另一名受试者在接受氟西汀（0.095）治疗后表现出低得多的比率。帕罗西汀（r2 = 0.404，p = 0.026）和舍曲林（r2 = 0.64，p = 0.002）的AD血浆浓度与DM / DXAD之间存在显着相关性，而氟西汀或文拉法辛则没有。此外，DM / DXAD与帕罗西汀，舍曲林和文拉法辛组的基线同工酶活性相关。这些结果表明，与舍曲林和文拉法辛相比，氟西汀和帕罗西汀对CYP2D6的抑制作用强而有力。 CYP2D6抑制可能部分与剂量，血浆浓度和基线同工酶活性有关，这些相关性值得进一步研究。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号