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在联用拉扎贝胺和吗氯贝胺期间的酪胺药效学。

Tyramine pharmacodynamics during combined administration of lazabemide and moclobemide.

作者信息

Dingemanse J, Hussain Y, Korn A

机构信息

Department of Clinical Pharmacology, F. Hoffmann-La Roche, Basel, Switzerland.

出版信息

Int J Clin Pharmacol Ther. 1996 Apr;34(4):172-7.

PMID:8861736
Abstract

The objective of this study was to assess the tyramine pressor sensitivity during combined administration of selective and reversible inhibitors of monoamine oxidase A and B, viz. moclobemide (300 mg b.i.d.) and lazabemide (100 mg b.i.d.), respectively. In part A, 5 healthy male subjects underwent i.v. tyramine pressor tests before (baseline) and during (day 7) combined treatment with both drugs. The tyramine dose was titrated until an increase in systolic blood pressure of 30 mmHg was attained. Subsequently, lazabemide treatment was discontinued and i.v. tyramine pressor tests were again conducted after 2 - 3 days of moclobemide monotreatment. The tyramine pressor sensitivity factor (mean + or - SD) during combined moclobemide and lazabemide treatment was 4.2 + or - 0.9 and during moclobemide monotreatment 3.1 + or - 1.1. In part B, a separate panel of 8 subjects received combined treatment with moclobemide and lazabemide for up to 10 days. Ascending oral doses of tyramine were administered on days 7 - 10 to determine the threshold dose eliciting a 30 mmHg increase in systolic blood pressure. In comparison to baseline the effects of oral tyramine were potentiated by a factor of 13.5 + or - 6.9. The low amount of oral tyramine needed (51 + or - 20 mg) to induce relevant increases in blood pressure indicates that dietary precautions are needed when both MAO-A and B are inhibited by 2 reversible inhibitors.

摘要

本研究的目的是评估在联合使用单胺氧化酶A和B的选择性可逆抑制剂即吗氯贝胺(300毫克,每日两次)和拉扎贝胺(100毫克,每日两次)期间的酪胺升压敏感性。在A部分,5名健康男性受试者在联合使用这两种药物之前(基线)和期间(第7天)接受静脉注射酪胺升压试验。酪胺剂量逐步滴定,直至收缩压升高30毫米汞柱。随后,停用拉扎贝胺治疗,在吗氯贝胺单药治疗2 - 3天后再次进行静脉注射酪胺升压试验。吗氯贝胺与拉扎贝胺联合治疗期间的酪胺升压敏感性因子(均值±标准差)为4.2±0.9,吗氯贝胺单药治疗期间为3.1±1.1。在B部分,另一组8名受试者接受吗氯贝胺和拉扎贝胺联合治疗长达10天。在第7 - 10天口服递增剂量的酪胺,以确定引起收缩压升高30毫米汞柱的阈剂量。与基线相比,口服酪胺的作用增强了13.5±6.9倍。诱导血压产生相关升高所需的口服酪胺量较低(51±20毫克),这表明当单胺氧化酶A和B都被两种可逆抑制剂抑制时,需要采取饮食预防措施。

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