6.3 Biological half-life by route of exposure
Under normal conditions, about 30% of amphetamine is
excreted unchanged in the urine but this excretion is highly
variable and is dependent on urinary pH. When the urinary pH
is acidic (pH 5.5 to 6.0), elimination is predominantly by
urinary excretion with approximately 60% of a dose of
amphetamine being excreted unchanged by the kidney within 48
hours. When the urinary pH is alkaline (pH 7.5 to 8.0),
elimination is predominantly by deamination (less than 7%
excreted unchanged in the urine); the half-life ranging from
16 to 31 hours (Ellenhorn, 1997).
6.4 Metabolism
The major metabolic pathway for amphetamine involves
deamination by cytochrome P450 to para-hydroxyamphetamine and
phenylacetone; this latter compound is subsequently oxidised
to benzoic acid and excreted as glucuronide or glycine
(hippuric acid) conjugate. Smaller amounts of amphetamine are
converted to norephedrine by oxidation. Hydroxylation
produces an active metabolite, O-hyroxynorephedrine, which
acts as a false neurotransmitter and may account for some
drug effect, especially in chronic users (Dollery, 1991).
6.5 Elimination and excretion
Normally 5 to 30% of a therapeutic dose of amphetamine
is excreted unchanged in the urine by 24 hours, but the
actual amount of urinary excretion and metabolism is highly
pH dependent (Dollery, 1991).
7. PHARMACOLOGY AND TOXICOLOGY
7.1 Mode of action
Amphetamine appears to exert most or all of its effect
in the CNS by causing release of biogenic amines, especialy
norepinephrine and dopamine, from storage sites in nerve
terminals. It may also slow down catecholamine metabolism by
inhibiting monoamine oxidase (Hardman, et al., 1997).
