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Food, drugs, and bioavailability.

The term "bioavailability" refers to that proportion of a drug which reaches the systemic circulation unchanged after a particular route of administration. When drugs are taken by mouth their bioavailability is determined by factors in the drug-which include the nature of the molecule, its stability, and the formulation administered'and in the patient-such as a reduced intestinal surface area as a result of coeliac disease or intestinal resection2 and whether or not the drug is taken with a meal. In addition, drugs may undergo "presystemic" metabolism in either the intestine,3 the liver,4 or, less commonly, the lungs. This "first pass" metabolism in the liver is important in limiting the bioavailability of many cardiovascular drugs, including several lipid soluble 13 adrenoceptor antagonists such as alprenolol, labetalol, metoprolol, and propranolol (possibly oxprenolol also) as well as the antiarrhythmic agents lignocaine and verapamil.5 Some tricyclic antidepressants and various opiate analgesics also undergo presystemic metabolism, but apparently some (perhaps half) of this process occurs in the intestinal wall.3 The same is true for the vasodilator hydralazine and other drugs which undergo N-acetylation. The extent of presystemic drug metabolism is frequently dose dependent,4 but other important influences include age, smoking habits, and concurrent drug treatment (which can modify microsomal enzyme activity).6 In addition, liver disease-especially cirrhosis-may lead to increased drug bioavailability as a result of diminished hepatic metabolism and shunting of blood through portosystemic anastomoses.7 Finally, food and other substances present in the diet can influence drug bioavailability.8 The first effect of food is to modify gastric emptying and so the rate of drug absorption. Because food may delay their absorption the oral hypoglycaemic agents glipizide and glibenclamide need to be given before breakfast.9 Secondly, cations in foodstuffs (principally calcium) will chelate with most tetracyclines to reduce their intestinal absorption. Thirdly, food may reduce absorption from the gastrointestinal tract of drugs which are partly ionised, hexamethonium and amiloride, for example. Other drugs whose absorption is impaired by food include the antihypertensives atenolol and captopril and the antituberculous compounds rifampicin and isoniazid.10 The long term ingestion of foods such as charcoal broiled hamburgers (which contain polycyclic hydrocarbons) may