When thyroidfunction is altered there are a series of physiological changes which are likely to affect drug absorption, metabolism or excretion, and altered pharmacokinetics have been described for a variety of drugs in both hypothyroidism and hyperthyroidism.Absorption of riboflavine is increased in hypothyroidism and decreased in hyperthyroidism due to changes in gut motility. Opposite/in dings have been described for ethanol in rats, but remain to be confirmed in man. There is definite evidence of induction of hepatic metabolism in hyperthyroidism with reduced metabolism in hypothyroidism. A ntipyrine half-lives are therefore decreased in hyperthyroidism and prolonged in hypothyroidism. The same may be true for aminopyrine, but there do not appear to be any significant changes iin phenytoin kinetics. There is need for an increased dose of oral anticoagulants in hypothyroidism and a decreased dose in hyperthyroidism due to altered catabolism of vitamin K -dependent clotting factors in the absence of any alteration in the metabolism of the anticoagulant drugs themselves. A t present it is not possible to predict the effect of altered thyroid function on the metabolism of any individual drug.The antithyroid drug methimazole, which is also the active metabolite of carbimazole,
has a shorter half-life in hyperthyroid patients than in normal controls. This probably accounts for the needforfrequent doses while hyperthyroidism is active and the effectiveness of a once daily dose once the disease is under control. Propylthiouracil has a shorter half-life than methimazole and there is litlle good evidence of any change in ha(f-I!fe with thyroid dysfunction.information about the ~-adrenoceptor blocking drugs in altered thyroid states is scanty, but there is a trend to a shortened propranolol ha(f-life and reduced area under the serum concentration-time curve in hyperthyroidism and a prolonged ha(f-life in hypothyroidism. The reasons for this will not be known untif propranolol metabolites are assayed in states of thyroid dysfunction. There is an increased clearance of practolol in hyperthyroidism, probably due to increased renal excretion.There are lower than normal plasma concentrations Qf cardiac glycosides in hyperthyroidism and, possibly, higher than normal concentrations in hypothyroidism. There appears to be an altered volume of distribution Qf digoxin in thyroid dysfunction -being increased in hyperthyroidism and decreased in hypothyroidism. This may be due to altered cardiac and skeletal muscle binding of digoxin in hyperthyroidism. Pharmacokinetic changes alone cannot
