MARTINEZ AND AMIDONUNDERSTANDING THE FACTORS AFFECTING DRUG ABSORPTIONPHARMACOKINETICS A D PHARMACODY AMICS PHARMACOKINETICS AND PHARMACODYNAMICS AMechanistic Approach to Understanding the Factors Affecting Drug Absorption: A Review of Fundamentals

A fundamental premise associated with the use of atherapeutic agent is that for any given patient, the clinical response can be predicted on the basis of the selected drug product, dose, and dosing regimen. This tenet provides the foundation for concepts of prescribability and switchability.1 Prescribability refers to an assumed relationship between a therapeutic out-come and the rate and extent of drug exposure. A physi-cian will prescribe a particular product in accordance with assumptions pertaining to this relationship. Generally, the process of drug movement from in-take (e.g., oral delivery systems) to its site of action can be schematically presented as follows (Figure 1). As depicted in Figure 1, the relationship between drug intake and a clinical response is highly complex, potentially affected by a host of intrinsic and extrinsic variables. Accordingly, deviations between drug re-sponse within or between individuals may be ascribed either to product bioavailability (i.e., the rate and extent of drug absorption), drug pharmacokinetics (which in-cludes themetabolism,distribution, andeliminationof a compound), or the particular concentration-effect relationship. While product formulation can significantly affect processes leading to drug absorption, once in the circu-lation, the original formulation is generally considered to no longer affect the ultimate drug response. In other words, it is the concentration of the drug moiety, along with its corresponding effect, that will ultimately de-termine product safety and effectiveness. For this rea-son, once a patient is titrated to a particular product anddosing regimen,we assume that a comparable clin-ical response will be achieved if the patient elects to take a less expensive generic equivalent. The purpose of this article is to discuss basic princi-ples associated with the process of drug absorption. Special attention will be given to the use of the Biopharmaceutics Classification System (BCS) as a predictive tool for identifying compounds whose ab-sorption characteristics may be sensitive to intrinsi