On average, about one half of a given dose is eliminated unchanged in the urine, while the other half is broken down into various metabolites (mostly benzoic acid).[42] However, the drug's half-life is highly variable because the rate of excretion is very sensitive to urinary pH. Under alkaline conditions, direct excretion is negligible and 95%+ of the dose is metabolized.[citation needed] Having an alkaline stomach will cause the drug to be absorbed faster through the stomach resulting in a higher blood level concentration of amphetamine. Having an alkaline bladder causes the drug to be excreted very slowly.[citation needed] The main metabolic pathway is:
dextroamphetamine \rightarrow \; phenylacetone \rightarrow \; benzoic acid \rightarrow \; hippuric acid.
Another pathway, mediated by enzyme CYP2D6, is:
dextroamphetamine \rightarrow \; p-hydroxyamphetamine \rightarrow \; p-hydroxynorephedrine.
Although p-hydroxyamphetamine is a minor metabolite (~5% of the dose), it may have significant physiological effects as a norepinephrine analogue.[43]
