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NUTRIENT DRUG INTERACTIONS

ities in both food and drug handling; (3) conditions, such as arthritis, that increase the likelihood that the person will be taking over-the-counter medications; (4) sex; (5) size and fat mass, which are related to a person’s diet and nutritional status; (6) exclusionary diets, for example, di- ets from which all animal products are excluded (vegan diets); (7) the use of substances of abuse, such as alcohol, which alter the handling of both drugs and nutrients; and finally, (8) medical conditions that require the care of dif- ferent specialists and multiple medications.

Effects of Foods and Food Components on Drug Absorption and Bioavailability

There are at least four ways in which foods and their components can affect the absorption and bioavailability of a drug:

• Physicochemical binding: The food component and the drug can bind to each other physicochemically, so that neither the drug nor the component can be ab- sorbed. For example, the antibiotic tetracycline binds with calcium, magnesium, iron, and zinc; once bound, the antibiotic becomes unavailable—that is why this drug should not be taken with dairy prod- ucts, which contain high amounts of these minerals.

• Stability: The food can alter the stability of the drug preparation in the stomach, so that it breaks down before it can be absorbed.

• Gastric emptying: The drug or food can change the rate at which the stomach empties, and therefore the rate at which the drug arrives in the small intestine. Gastric emptying is normally a three-phase process. When you begin to eat, a small amount of food mixed with stomach juices enters the small intestine. The presence of this mixture makes the small intestine send a signal to slow down gastric emptying. This slow-down allows the stomach time to thoroughly mix the food with the stomach juices, and to break down the food into small particles. Fatty foods are highly effective in slowing stomach emptying, while erythromycin, an antibiotic, increases the speed of gastric emptying.

A drug taken on an empty stomach is likely to be dumped rapidly into the small intestine. As a result, there will be only one peak in the curve describing the con- centration of the drug in the blood across time. By con- trast, a drug taken with food will arrive in the small intestine more slowly, and in small spurts (via the second phase of gastric emptying), so that there may be two or more peaks in this curve. Remember, though, that one job of the stomach is to break down pills into particles. If you take a pill on an empty stomach, it may arrive in the small intestine more quickly, but it may not be ab- sorbed if the pill is not sufficiently broken up. Further- more, a drug taken on an empty stomach will pass more rapidly through the small intestine, with the result that the time for absorption is shorter and less of the drug

ENCYCLOPEDIA OF FOOD AND CULTURE

may be absorbed. Finally, in the third phase of gastric emptying, approximately every 24 hours, the normal stomach has a massive series of contractions that propel larger particles and any remaining material in the stom- ach into the small intestine. If there are any large drug particles left behind in the stomach, this “housekeeping” emptying may lead to a sudden dumping of a large quan- tity of the drug into the small intestine, with a corre- sponding sharp peak in the blood concentration of the drug. The duration and extent of the phases of gastric emptying in response to food vary considerably from in- dividual to individual, but is longer in women than in men, and is much longer in chronic alcoholics. Smoking while eating also delays stomach emptying.

The fourth way in which foods can affect the ab- sorption and bioavailability of a drug is by:

• Competition for absorption: Many drugs use the intes- tine’s natural transport systems—which normally transport food components—to cross the intestinal wall. They therefore compete with food components for transport. For example, L-dopa and methyldopa (drugs used to control Parkinson’s disease) use the same transporter mechanism as aromatic amino acids from proteins, so absorption of these drugs is de- creased if you eat a high-protein meal at the same time you take the drug.

In general, we can divide drugs into those that are best absorbed on an empty stomach (for example, most but not all antibiotics, digitalis preparations, captopril, and sucralfate); those absorbed best with food (for ex- ample, some hypertension medications such as chloroth- iazide and spironolactone, and drugs for blood lipid abnormalities such as lovastatin and gemfibrozil), and those for which absorption varies by the type of prepa- ration or formulation. For example, drugs that are en- terically coated (so that they are not destroyed by stomach acid) may be more easily absorbed if they are taken with food, because a long stay in the stomach may weaken the coating just enough that it disintegrates more easily in the small intestine.

The examples given above are general rules and may not be true for the specific preparation you may be tak- ing. Therefore, it is critical to check the package insert for your drug and to consult with your pharmacist. For example, theophylline, a commonly used asthma drug, comes in several different formulations, depending on the manufacturer. One version of theophylline is best ab- sorbed when accompanied by a high-fat meal, while an- other is poorly absorbed. The rate of absorption of theophylline is extremely important because it is one of the many drugs that has a narrow therapeutic window; in other words, there is a very small difference between the concentration of drug that you need in your bloodstream for it to be effective, and the concentration at which the drug becomes toxic. For the drug to work properly, it is critical to maintain a steady level of the drug in the

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