The clinical pharmacology of intranasal l-methamphetamine.

John E Mendelson, Dana McGlothlin, Debra S Harris, Elyse Foster, Tom Everhart, Peyton Jacob, Reese T Jones
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引用次数: 81

Abstract

Background: We studied the pharmacology of l-methamphetamine, the less abused isomer, when used as a nasal decongestant.

Methods: 12 subjects self-administered l-methamphetamine from a nonprescription inhaler at the recommended dose (16 inhalations over 6 hours) then at 2 and 4 (32 and 64 inhalations) times this dose. In a separate session intravenous phenylephrine (200 microg) and l-methamphetamine (5 mg) were given to define alpha agonist pharmacology and bioavailability. Physiological, cardiovascular, pharmacokinetic, and subjective effects were measured.

Results: Plasma l-methamphetamine levels were often below the level of quantification so bioavailability was estimated by comparing urinary excretion of the intravenous and inhaled doses, yielding delivered dose estimates of 74.0 +/- 56.1, 124.7 +/- 106.6, and 268.1 +/- 220.5 microg for ascending exposures (mean 4.2 +/- 3.3 microg/inhalation). Physiological changes were minimal and not dose-dependent. Small decreases in stroke volume and cardiac output suggesting mild cardiodepression were seen.

Conclusion: Inhaled l-methamphetamine delivered from a non-prescription product produced minimal effects but may be a cardiodepressant.

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l-甲基苯丙胺鼻内的临床药理学研究。
背景:我们研究了l-甲基苯丙胺的药理学,这是一种较少被滥用的异构体,当用作鼻减充血剂时。方法:12名受试者从非处方吸入器中以推荐剂量(6小时内吸入16次)自我给予l-甲基苯丙胺,然后分别以推荐剂量的2倍和4倍(32倍和64倍)吸入。在一个单独的疗程中,静脉注射苯肾上腺素(200微克)和l-甲基苯丙胺(5毫克)来确定α激动剂的药理学和生物利用度。测量了生理、心血管、药代动力学和主观效应。结果:血浆l-甲基苯丙胺水平通常低于定量水平,因此通过比较静脉和吸入剂量的尿排泄来估计生物利用度,得出上升暴露的交付剂量估计为74.0 +/- 56.1,124.7 +/- 106.6和268.1 +/- 220.5微克(平均4.2 +/- 3.3微克/吸入)。生理变化很小,不依赖于剂量。卒中量和心输出量的小幅下降表明轻度心脏抑制。结论:从非处方产品中吸入l-甲基苯丙胺产生的影响很小,但可能是一种心脏抑制剂。
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