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d-Methamphetamine, the N-methyl derivative of amphetamine, was first synthesized in 1919. Methamphetamine is available in the d- and l-forms. The d-form has reportedly greater central stimulant activity than the l-isomer, which has greater peripheral sympathomimetic activity. The d-form is the commonly abused form while the l-isomer is typically found in non-prescription inhalers as a decongestant.

Although initially available as an injectable solution for the treatment of obesity, d-methamphetamine hydrochloride is currently available as conventional and prolonged release tablets. Illicit methamphetamine is synthesized from the precursors phenylacetone and N-methylformamide (dl mixture) or alternatively from ephedrine by red phosphorus/acid reduction. Absorption

Doses of 5 to 10 mg methamphetamine typically result in blood concentrations between 20 to 60 ng/mL. In one study,10 six healthy adults were orally administered a single dose of 0.125 mg/kg methamphetamine. Peak plasma concentrations were achieved at 3.6 h with a mean concentration of 20 ng/mL. In a second study, Lebish et al.11 observed a peak blood concentration of 30 ng/mL, 1 h after a single oral dose of 10 mg methamphetamine to one subject. Metabolism and Excretion

In humans, both the d- and l-forms undergo hydroxylation and N-demethylation to their respective p-hydroxymethamphetamine and amphetamine metabolites. Amphetamine is the major active metabolite of methamphetamine. Under normal conditions, up to 43% of a d-methamphetamine dose is excreted unchanged in the urine in the first 24 hours and 4 to 7% will be present as amphetamine. In acidic urine, up to 76% is present as parent drug10 compared with 2% under alkaline conditions. Approximately 15% of the dose was present as p-hydroxymethamphetamine and the remaining minor metabolites were similar to those found after amphetamine administration. Urine concentrations of methamphetamine are typically 0.5 to 4 mg/L after an oral dose of 10 mg. However, methamphetamine and amphetamine urine concentrations vary widely among abusers. Lebish et al.11 reported urine methamphetamine concentrations of 24 to 333 mg/L and amphetamine concentrations of 1 to 90 mg/L in the urine of methamphetamine abusers.

l-Methamphetamine is biotransformed in a similar manner to the d-isomer but at a slower rate. Following a 13.7 mg oral dose, the 24 h urine contained an average of 34% of the dose as l-methamphetamine and 1.7% of the dose as l-amphetamine.3

d-Methamphetamine is commonly self-administered by the smoked route. Both the freebase and hydrochloride salt of methamphetaime are volatile and > 90% of parent drug can be recovered intact when heated to temperatures of 300°C. When cigarettes containing tobacco mixed with methamphetamine were pyrolyzed, amphetamine, phenylacetone, dimethylam-phetamine, and N-cyanomethyl methamphetamine were the major resulting products.12 Cook13


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