The Clinical Pharmacology of Intranasal l-Methamphetamine

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 μg) and l-methamphetamine (5 mg) were given to define alpha agonist pharmacology and bioavailability. Physiological, cardiovascular, pharmacokinetic, and subjective effects were measured.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 μg for ascending exposures (mean 4.2 ± 3.3 μg/inhalation). Physiological changes were minimal and not dose-dependent. Small decreases in stroke volume and cardiac output suggesting mild cardiodepression were seen.Inhaled l-methamphetamine delivered from a non-prescription product produced minimal effects but may be a cardiodepressant.There are two enantiomers of methamphetamine: dextrorotatory (d) methamphetamine and levorotatory (l) methamphetamine. The d-isomer is commonly abused and is available by prescription (DEA Schedule II), but unknown to most physicians the l-isomer is sold over-the-counter and is the active ingredient of the Vicks？ Vapor Inhaler (spelled levmetamfetamine by the manufacturer, Procter & Gamble, Cincinnati, OH) [1,2]. Each Vicks inhaler contains about 50 mg of l-methamphetamine, and earlier estimates suggested delivered daily doses between 1.9 to 7.2 mg of drug when used as directed [3]. The over-the-counter (OTC) vasoconstrictor nasal decongestant phenylpropanolamine (PPA) was associated with an increased risk of hemorrhagic stroke in young women that led to it being voluntarily withdrawn from the market [4]. Ephedra, another component of OTC nasal decongestants may also increase the risk of cardiovascular adverse events [5]. Methamphetamine is a sympathomimetic