Final answer:
The simplest factor in determining drug distribution is the drug's binding to plasma proteins.
Step-by-step explanation:
The simplest factor in determining drug distribution is the drug's binding to plasma proteins. The concentration of a drug that is not bound to plasma proteins is the active form of the drug that can cross membrane barriers, distribute to tissues, and exert its effects. Only the unbound drug is available to produce pharmacological and toxicological effects.