Because levothyroxine (T4) treatment is frequently needed in clinical practice, it is important to consider the issue of T4's bioavailability when it is given orally. T4 absorption has been estimated by a variety of techniques. In normal human subjects, 60% to 80% of oral T4 generally enters the central circulation after oral administration, but there is considerable variability among subjects and in repeated studies of the same subject. The present review discusses those factors that affect intestinal absorption of orally administered T4, thus influencing its bioavailability. In addition to absorption factors, the effectiveness of an oral T4 dose may also be affected by postabsorption factors such as alterations in the metabolic clearance rate of endogenous T4, or biliary secretion of absorbed T4 before it can enter the general circulation. A variety of clinical conditions have been shown to influence T4 absorption. On the average, absorption efficiency is increased in hypothyroidism and hyperthyroidism, and also in patients who have undergone gastrojejunostomy. The average T4 absorption decreases slightly after age 70. It is markedly decreased in conditions in which there is a decrease in the effective small intestinal absorptive surface, including short bowel syndromes sprue, and other malabsorptive conditions. Sterilization of the bowel leads to increased T4 absorption, probably due to increased absorption by the colon, which ordinarily plays a negligible role in T4 absorption. The intraluminal milieu within the small intestine is the most important influence on T4 absorption in persons without small bowel disease. Food has been shown to decrease T4 absorption efficiency, and it is improved in the fasting state. Certain specific thetary factors are especially important in impairing absorption, including walnuts, cotton seed meal, liver residue, albumin, and soybean infant formula. Certain medications such as cholestyramine and colestipol, and probably other bile sequestration agents, also inhibit T4 absorption, as do oral iron preparations. The iron effect is enhanced by increased gastric pH, and achlorhydria alone is associated with reduced T4 bioeffectiveness. Other drugs associated with decreased intestinal absorption of T4 include charcoal, diphenylhydantoin, propanolol, and sucralfate
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