Linezolid, a novel oxazolidinone antibiotic: Assessment of monoamine oxidase inhibition using presser response to oral tyramine
Linezolid, a novel oxazolidinone antibiotic: Assessment of monoamine oxidase inhibition using presser response to oral tyramine
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DOI：
10.1177/00912700122010294
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发表时间：
2001-05-01
影响因子：
2.9
通讯作者：
Donaldson, KM
中科院分区：
文献类型：
--
作者：
Antal, EJ;Hendershot, PE;Donaldson, KM
这项研究的主要目的是比较口服利奈唑胺、吗氯贝胺和安慰剂对口服酪胺的血压反应的影响。次要目标是根据酪胺的药代动力学变化确定可能的作用机制，并评估量化压力效应的替代方法。受试者服用利奈唑胺(625毫克，每日2次)、吗氯贝胺(150毫克，每日3次)或安慰剂，疗程长达7天。使用口服酪胺剂量使收缩压(SBP)升高30 mmHg(PD>；30)，阳性升压反应被定义为PD>；30指数(PD>；30的治疗前/治疗比率)大于或等于2。分别有8/10、11/11和1/10的利奈唑胺、吗氯贝胺和安慰剂的应答者在停药一天内反应恢复到基线。平均最大体感诱发电位与最大体感诱发电位时心率的比值(GSBP/HR)随着酪胺剂量的增加而线性增加，利奈唑胺和吗氯贝胺治疗期间也是如此。在治疗期间，服用利奈唑胺或吗氯贝胺的受试者对酪胺的反应与安慰剂显著不同。与安慰剂相比，这两种药物都显著降低了酪胺的口服清除量。尿儿茶酚胺和代谢物的排泄与药物的MAOI活性一致，但结果不同。利奈唑胺的MAOI活性与吗氯贝胺相似，吗氯贝胺是一种临床上无食物限制的药物。服用利奈唑胺时，不应限制含酪胺食物的正常饮食摄入量。(C)2001年美国临床药理学会。
The primary objective of this study was to compare the effects of oral linezolid with moclobemide and placebo on the presser response to oral tyramine. Secondary objectives were to determine possible mechanisms of the effect based on changes in the pharmacokinetics of tyramine and to evaluate alternative methods for quantifying the presser effect. Subjects received linezolid (625 mg bid orally) moclobemide (150 mg tid orally), or placebo for up to 7 days. Using the oral tyramine dose producing a > 30 mmHg increase in systolic blood pressure (SBP) (PD> 30), a positive presser response was defined as a PD> 30 index (pretreatment/treatment ratio of PD> 30) of greater than or equal to 2. There were 8/10, 11/11, and 1/10 responders with linezolid, moclobemide, and placebo, respectively Responses returned to baseline within a days of drug discontinuation. The ratio of mean greatest SEP and heart rate at the time of greatest SEP (GSBP/HR) increased linearly with tyramine dose both pretreatment and during treatment with linezolid and moclobemide. During treatment, responses to tyramine when subjects took linezolid or moclobemide were significantly different from placebo. Both drugs significantly decreased tyramine oral clearance compared with placebo. Urinary excretion of catecholamines and metabolites was consistent with MAOI activity of the drugs, but results were variable. The MAOI activity of linezolid is similar to that of moclobemide, a drug used clinically without food restrictions. Restrictions to normal dietary intake of tyramine-containing foods are not warranted when taking linezolid. (C) 2001 the American College of Clinical Pharmacology.