ABSTRACT
INTRODUCTION The human gut has evolved over many thousands of years to provide an efficient system for the extraction of nutrients contained in a highly variable food supply. Within the mix of grain, meat, and berries, which formed the diet of ancestral mammals, poisonous seeds and berries were accidentally ingested and protective responses to the unwanted pharmacology were developed. Spitting out bitter materials and vomiting provided some level of protection for higher mammals, and intestinal mechanisms were developed to reduce exposure. Thus, the physiology of the digestive process is less than convenient for the efficient absorption of many of the modern therapeutic entities, which resemble such poisons. In addition, we differ in our genetic and social patterns, which in turn impact on the efficiency of absorption and clearance and, therefore, the time course of the effects that we see with medications. Variability in the plasma concentration-time profile within and between individuals can be strongly influenced by anatomical, physiological, physicochemical, and biochemical factors including nature of the mucosa, the available surface area, pH, and the presence of enzymes and bacteria. In particular, the influence of feeding and temporal patterns on gastrointestinal (GI) transit is of great relevance as a factor in the absorption of poorly soluble drugs.
