Drug absorption in gastrointestinal disease with particular reference to malabsorption syndromes.

There is a considerable range in the dose of many drugs that is required to produce a given pharmacological effect in an individual patient. This individual variation in dose requirement is sometimes reflected in the wide scatter in the steady state plasma concentration that follows the same oral dose of a drug given to any group of subjects. Such individual differences are largely due to variation in the rate of elimination of drugs. Gastrointestinal disease may also alter oral dose requirements by producing variation in both the amount and rate of drug absorption. These changes may be reflected in the plasma concentration/time curve that follows an oral dose. The amount of drug abosorbed is simultaneously affected by many factors. These include the physicochemical properties of the drug and the physiological factors that operate within the gut, as well as the presence of other substances such as food, or interaction with other drugs in the gut. The availability of the drug within the intestinal lumen is largely governed by its dissolution characteristics, particularly factors which can interfere with dissolution of the drug product in the gut. Physiological factors within the gut that affect oral drug absorption include gastric emptying rate and intestinal motility, the pH of the gastrointestinal fluids, the activity of gastrointestinal drug metabolising enzymes (e.g. monoamine oxidase and dopa decarboxylase) or drug metabolising bacteria and the surface area of the gut. Many factors affect gastric emptying. These include disease, surgery and other drugs. A change in the rate of gastric emptying alters the rate of drug delivery from the stomach to the duodenum and upper small intestine. This may profoundly alter the plasma concentration/time curve that follows oral administration of many drugs. For some drugs, proximal jejunal disease may reduce, delay or increase the apparent amount of drug absorbed. Reduced absorption of an antibiotic leads to a fall in the peak plasma concentration. If the peak falls below the minimum inhibitory concentration for a particular organism then therapeutic failure may occur, if it is assumed that the peak plasma concentration is all important for antimicrobial activity. Excessive drug absorption may lead to drug toxicity. Abnormal drug absorption is a feature of lower small intestinal conditions such as Crohn's disease. This suggests that drug absorption is not confined to the jejunum but continues throughout the small intestine. It is not always possible to predict the pattern of drug malabsorption from a knowledge of the physicochemical and pharmacokinetic properties of the drug and the pathophysiology of the disease. The rate and amount of drug absorbed be one patient may differ from that in another patient with the same condtion. Although these differences reflect normal individual variation, they are also related to the extent and activity of disease at the time of study...