Metabolism of amphetamine
is highly dependent on pH levels because amphetamine has a relatively high pKa constant of 9.8-9.9. Now SWIM
must explain pKa values the best he can (he is not a chemistry major after all):
Ka = acid dissociation constant or acid ionization constant
We will refer to it as the acid ionization constant because it makes understanding this a bit easier. Now, these values are most often seen described as pKa values because the Ka values range greatly over many different magnitudes and so:
pKa = 10^(Ka)
This thankfully brings the value range into the area of -100 to 100 for extreme cases, though most pKa values are rather between about -10 and 10. Now, we must understand how drugs
are absorbed. When taken orally technically drugs can begin absorption in the mouth, this is why LSD
and other drugs can be put under the tongue, however most of the absorption occurs in the small intestine. The drug
then travels to the liver, being metabolized along the way into other chemicals, and then to the bloodstream.
Well this is where pH and pKa levels have everything to do with absorption and it comes back to that key term ionization. When amphetamines become ionized they a) become more attracted to water and b) become less lipid soluble. So the ionized amphetamine is water-soluble while the non-ionized is lipid soluble. Amphetamine needs to be lipid-soluble to get into important membranes and inversely water soluble to get out. Since it is a base amphetamine will ionize acids and be non-ionized at varying percentages closer to a pH of 9.8 (the pKa level of amphetamine).
So, firstly this can inhibit absorption. If pH levels are high in the duodenum where amphetamine (and most drugs) are absorbed then a higher percentage of amphetamine will be ionized this will inhibit absorption. If inhibited long enough you will lose some of the amphetamine. Result: blood plasma levels are lower and the drug is thus less potent.
More importantly to the thread starter, pKa effects drug elimination. When the amphetamine is traveling through the bloodstream after absorption, acidic urine and an acidic enviroment ionize the amphetamine and speed up bodily elimination of the drug. This results in shorter duration.
Info about amphetamines and pH levels can be found here: