Bioavailability is the fraction of the dose of drug that reaches the systemic circulation. By mouth simple solutions of drugs usually have the highest bioavailability, and for that reason are sometimes used for the first administration. Later in the development programme, tablets or capsules are more often used, and relative bioavailability studies are needed to compare the performance of the new with the original formulation. If the drug is very rapidly eliminated from the body, a sustained release formulation may be required; such formulations are usually tested in Phase I studies before progression to studies of efficacy in patients.

Absolute bioavailability is determined by comparing blood concentrations of drug after intravenous dosing with those after dosing by the oral or other route. Although it is helpful to know the absolute bioavailability of a new drug, it is not essential. Absolute bioavailability studies are often omitted because of the time and expense of developing an intravenous formulation; the drug cannot be given intravenously unless the toxicity of the drug by that route has been studied in animals.

It has long been recognize that some foods and drugs, when taken during the same period of time, can alter the body's ability to utilize a particular food or drug, or cause serious side effects. Certain foods (grapefruit), beverages, alcohol, caffeine, and even cigarettes can interact with IMPs/NCEs. This may make them less effective or may cause dangerous side effects or other problems.