Plasma and urinary concentrations of methamphetamine after oral administration of famprofazone to man

Abstract

1. To obtain further evidence for the metabolic formation of methamphetamine from famprofazone in man, concentrations of methamphetamine in plasma, as well as in urine, were measured by g.l.c. In addition, intact famprofazone and famprofazone N-oxide were analysed in the urine.

2. Methamphetamine appeared in plasma 1 h after a single 100mg dose of the drug to two male subjects, and the concentration maintained between 24 and 44ng/ml over 2-12 h, declining to 10ng/ml and an undetectable level respectively after 24 h.

3. Total urinary excretion of methamphetamine over 72 h was 1·9mg for a 25 mg dose and 2·2mg for a 50mg dose. After a 100mg dose, 4·6 mg of methamphetamine was excreted over 36h. Neither intact famprofazone nor famprofazone N-oxide were detected when the urine samples after the 100mg dose were examined.

4. The results provide further evidence that methamphetamine is a bona fide human metabolite of famprofazone and suggest that at least 20% dose may be broken down via the pathways leading to the formation of methamphetamine. This could have significant clinical implications as the result of pharmacological activity of this metabolite.