...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Pharmacological research: The official journal of The Italian Pharmacological Society >Methadone-metabolism, pharmacokinetics and interactions.
【24h】

Methadone-metabolism, pharmacokinetics and interactions.

机译：美沙酮代谢，药代动力学和相互作用。

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 pharmacokinetics of methadone varies greatly from person to person; so, after the administration of the same dose, considerably different concentrations are obtained in different subjects, and the pharmacological effect may be too small in some patients, too strong and prolonged in others. Methadone is mostly metabolised in the liver; the main step consists in the N-demethylation by CYP3A4 to EDDP (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine), an inactive metabolite. The activity of CYP3A4 varies considerably among individuals, and such variability is the responsible for the large differences in methadone bioavailability. CYP2D6 and probably CYP1A2 are also involved in methadone metabolism. During maintenance treatment with methadone, treatment with other drugs may be necessary due to the frequent comorbidity of drug addicts: psychotropic drugs, antibiotics, anticonvulsants and antiretroviral drugs, which can cause pharmacokinetic interactions. In particular, antiretrovirals, which are CYP3A4inducers, can decrease the levels of methadone, so causing withdrawal symptoms. Buprenorphine, too, is metabolised by CYP3A4, and may undergo the same interactions as methadone. Since it is impossible to foresee the time-lapse from the administration of another drug to the appearing of withdrawal symptoms, nor how much the daily dose of methadone should be increased in order to prevent them, patients taking combined drug treatments must be carefully monitored. The so far known pharmacokinetic drug-drug interactions of methadone do not have life-threatening consequences for the patients, but they usually cause a decrease of the concentrations and of the effects of the drug, which in turn can cause symptoms of withdrawal and increase the risk of relapse into heroin abuse.
机译：美沙酮的药代动力学因人而异。因此，在给予相同剂量后，在不同的受试者中获得的浓度明显不同，并且某些患者的药理作用可能太小，而其他患者的药理作用可能太强而时间更长。美沙酮主要在肝脏中代谢。主要步骤是通过CYP3A4将N-去甲基化为非活性代谢物EDDP（2-亚乙基-1,5-二甲基-3,3-二苯基吡咯烷）。 CYP3A4的活性在个体之间差异很大，而这种变异性是导致美沙酮生物利用度差异很大的原因。 CYP2D6和可能的CYP1A2也参与美沙酮的代谢。在美沙酮维持治疗期间，由于吸毒者的常见合并症，可能有必要使用其他药物进行治疗：精神药物，抗生素，抗惊厥药和抗逆转录病毒药物，它们可能引起药代动力学相互作用。特别是作为CYP3A4诱导剂的抗逆转录病毒药物可以降低美沙酮的水平，从而引起戒断症状。丁丙诺啡也被CYP3A4代谢，可能与美沙酮发生相同的相互作用。由于无法预见从服用另一种药物到出现戒断症状所需的时间，也无法预知美沙酮的每日剂量应增加多少以防止它们出现，因此，必须仔细监测接受联合药物治疗的患者。到目前为止，美沙酮的药代动力学药物-药物相互作用对患者没有致命的后果，但它们通常会导致药物浓度和作用降低，进而会导致停药症状并增加再次滥用海洛因的风险。

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