AMFEXA Tablet Ref.[27655] Active ingredients: Dexamfetamine

Absorption

Dexamfetamine is highly lipophilic and rapidly absorbed from the gastrointestinal tract. The pharmacokinetics of the tablets was measured in 18 healthy subjects. Following the administration of one 5-mg tablet of Amfexa 5 mg Tablets, average maximal plasma concentrations (C_max) of 11.5 ng/mL were achieved at approximately 1.5 hours.

Distribution

Following oral intake, amfetamines are rapidly distributed to major organ systems. Amfetamines are highly liposoluble and can cross the blood-brain barrier. Concentrations reached in the central nervous system may be 8 times higher than plasma levels. The plasma binding of amfetamine averages between 15 and 34%.

Biotransformation

The biotransformation of amfetamine takes place in the liver and mainly comprises hydroxylation and conjugation with glucuronic acid leading to more hydrophilic components which can be more easily eliminated. Smaller amounts of amfetamine are converted to norephedrine by oxidation. Hydroxylation produces an active metabolite (p-hydroxynorephedrine) which acts as a false neurotransmitter and may account for some drug effects, especially in chronic users.

Elimination

Amfetamine is primarily excreted in the urine; however, tubular reabsorption is relatively high due to its lipophilic properties. The elimination of amfetamine is pH-dependent, i.e. at low pH about 80% of the amfetamine may be eliminated in the unaltered form within 24 hours; in alkaline urine, there are only 2–3% of the amfetamine which will be eliminated as free amfetamine. The extent of bioavailability of the tablets was measured in 18 healthy subjects. The average plasma half-life (t_1/2) was 10.2 hours.

Animal studies on general toxicity, safety pharmacology, genotoxicity and carcinogenicity of dexamfetamine did not reveal any adverse effects not already known in humans.

In studies on the reproductive toxicity of dexamfetamine in mice an increased risk of malformations was observed, but only at doses 41 times the human dose. In rats treated with a dose corresponding to 12.5 times the human dose and rabbits treated with doses of dexamfetamine corresponding to up to 7 times the human dose no embryotoxic effects were observed.

Behavioural studies in rodents revealed developmental delay, behavioural sensitization as well as increased motor activity in offspring after prenatal exposures to dexamfetamine at dose levels comparable to human therapeutic dose levels. The clinical relevance of these findings is unknown.