Author Marianne Ashford
The gastrointestinal tract is complex and many physiological factors affect absorption of drugs as they transit through the tract, physiological factors affecting absorption include the transit of dosage forms through the gastrointestinal tract, environmental factors, such as the pH, enzymes and food within the gastrointestinal tract and disease states of the gastrointestinal tract, barriers to drug absorption include environmental factors, such as pH and enzymes, the mucus and unstirred water layer, the gastrointestinal membrane and pre-systemic metabolism, drugs are absorbed through the gastrointestinal membrane via either transcellular, paraceullular or active transport processes. factors that influence the rate and extent of absorption depend upon the route of administration, absorption will depend on the physiology of the administration site(s) and the membrane barriers present at those site(s) that the drug needs to cross in order to reach the systemic circulation, over 80% of medicines being given by mouth, rate-limiting step, controls the overall rate and extent of appearance of intact drug in the systemic, rate-limiting step will vary from drug to drug. For a drug which has a very poor aqueous solubility, the rate at which it dissolves in the gastrointestinal fluids is often the slowest step and the bioavailability of that drug is said to be dissolution-rate limited. In contrast, for a drug that has a high aqueous solubility, its dissolution will be rapid and the rate at which the drug crosses the gastrointestinal membrane may be the rate-limiting step termed permeability limited, Other potential rate-limiting steps include the rate of drug release from the dosage form (this can be by design, in the case of controlled-release dosage forms), the rate at which the stomach empties the drug into the small intestine, the rate at which the drug is metabolized by enzymes in the intestinal mucosal cells during its passage through them into the mesenteric blood vessels, and the rate of metabolism of drug during its initial passage through the liver, often termed the first-pass effect, small intestine is the major site of drug absorption, sustained- or controlled-release drug delivery systems
