[10] Pharmacodynamic tolerance begins when the cellular response to a substance is reduced with repeated use.
[14] Pharmacokinetics refers to the absorption, distribution, metabolism, and excretion of drugs (ADME).
All psychoactive drugs are first absorbed into the bloodstream, carried in the blood to various parts of the body including the site of action (distribution), broken down in some fashion (metabolism), and ultimately removed from the body (excretion).
All of these factors are very important determinants of crucial pharmacological properties of a drug, including its potency, side effects, and duration of action.
This type of tolerance is most evident with oral ingestion, because other routes of drug administration bypass first-pass metabolism.