Although LADME processes generally follow the above sequence, these are not discrete events. That is, one process is still occurring while the next one begins. Each event continues to occur well into the next. In fact, all five processes may occur simultaneously. Consider the case of a sustained release drug, the core of the SR tablet may still be liberating drug while previously absorbed drug is being eliminated.

LADME processes can be divided into two classes, drug input and drug output.

Input processes are:

• L = Liberation, the release of the drug from it's dosage form.
• A = Absorption, the movement of drug from the site of administration to the blood circulation.

The term commonly used to describe the rate and extent of drug input is bioavailability. Drugs administered by intravenous routes exhibit essentially 100% bioavailability.

Output processes, or disposition of drug are:

• D = Distribution, the process by which drug diffuses or is transferred from intravascular space to extravascular space (body tissues).
• M = Metabolism, the chemical conversion or transformation of drugs into compounds which are easier to eliminate.
• E = Excretion, the elimination of unchanged drug or metabolite from the body via renal, biliary, or pulmonary processes.

Because our main focus is on IV administered drugs, the remainder of this review will concentrate on output processes.

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Section 1 - Pharmacokinetic Concepts

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