Summary
Thyroid dysfunction can influence the physiological disposition of drugs. Depending on the pharmacokinetic properties of the individual drug, changes in the rate of metabolism ranging from profound to moderate or negligible have been observed. Since renal function is also influenced by thyroid disease, changes in renal elimination of drugs which are excreted in the urine mainly as unchanged drugs have to be considered as another reason for altered drug disposition in thyroid disease.
In patients with thyrotoxicosis, lower, and in patients with myxoedema, higher, digitalis plasma levels have been observed. The altered disposition of cardiac glycosides in thyroid dysfunction can be attributed to changes in renal elimination and metabolism. These findings may be the kinetic correlate for the clinical observation that larger than the usual dose of digitalis is required in thyrotoxic patients and lower in hypothyroid patients.
Antipyrine half-lives are very much shortened during hyperthyroidism and prolonged appreciably during hypothyroidism. The alterations in the disposition of these drugs seen during thyroid dysfunction can be ascribed to changes in its rate of metabolism which is controlled by the levels of circulating thyroid hormones. N-demethylation of aminopyrine is depressed both in hyper- and hypothyroid patients as compared with euthyroid subjects. Changes in the half-life of this drug were observed only during hypothyroidism. The physiological disposition of the antithyroid drug propylthiouracil is not changed during thyrotoxicosis. A decrease in plasma half-life of methimazole is however, observed during hyperthyroidism, whereas in hypothyroid patients half-life is increased.
The few data available so far do not allow general prediction of how thyroid disease could alter drug metabolism in man.
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Barker, P.S.; Bohning, A.L. and Wilson, F.N.: Auricular fibrillation in Grave’s disease American Heart Journal 8: 121–127 (1932).
Boas, E.P.: Digitalis dosage in auricular fibrillation American Heart Journal 6: 788–803 (1931).
Brunk, S.F.; Combs, S.P.; Miller, J.D.; Delle, M. and Wilson, W.R.: Effects of hypothyroidism and hyperthyroidism on dipyrone metabolism in man. Journal of Clinical Pharmacology 14: 271–279 (1974).
Buccino, R.A.; Spann, J.R.; Pool, P.E.; Sonnenblick, E.H. and Braunwald, E.: Influence on the thyroid state on the intrinsic contractile properties and energy stores of the myocardium. Journal of Clinical Investigation 46: 1669–1682 (1967).
Carrier, R.N. and Buday, P.V.: Augmentation of toxicity of monoamine oxidase inhibitor by thyroid feeding. Nature 191: 1107 (1961).
Conney, A.H. and Garren, L.: Contrasting effects of thyroxin on zoxazolamine and hexobarbital metabolism. Biochemical Pharmacology 6: 257–262 (1961).
Coville, P.F. and Telford, J.M.: Changes in drug sensitivity in hyperthyroidism British Journal of Pharmacology 36: 189P (1969).
Crooks, J.; Hedley, A.J.; MacNee, C. and Stevenson: Changes in drug metabolizing ability in thyroid disease. British Journal of Pharmacology 49: 156 P–157P (1973).
Croxson, M.S. and Ibbertson, H.K.: Serum digoxin in patients with thyroid disease. British Medical Journal 3: 566–568 (1975).
Doherty, J.E. and Perkins, W.H.: Digoxin metabolism in hypo- and hyperthyroidism. Studies with tritiated digoxin in thyroid disease. Annals of Internal Medicine 64: 489–507 (1966).
Eichelbaum, M.; Bodem, G.; Gugler, R.; Schneider-Deters, Ch. and Dengler, H.J.: Influence of thyroid status on plasma half-life of antipyrine in man. New England Journal of Medicine 290: 1040–1042 (1974).
Eichelbaum, M.; Bodem, G. and Schneider-Deters, Ch.: Antipyrine half-life time, antipyrine metabolism and thyroid function in man. Naunyn-Schmiedeberg’s Archives of Pharmacology. Suppl. 277, R 14 (1973).
Eichelbaum, M.; Schomerus, M.; Spannbrucker, N. and Zietz, E.: The physiological disposition of 14-C antipyrine in man. Naunyn-Schmiedeberg’s Archives of Pharmacology, Suppl. 293, R 251 (1976).
Eickenbusch, W.; Lahrtz, Hg; Seppelt, U. and van Zwieten, P.A.: Serum concentration and urinary excretion of 3H-ouabain and 3H-digitoxin in patients suffering from hyperthyroidism or hypothyroidism. Klinische Wochenschrift 48: 270–275 (1969).
Ellinwood, E.H. and Prange, A.J.: Effect of epinephrine pretreatment on pentobarbital sleeping time of mice with altered thyroid status. Nature 201: 305–306 (1964).
Frye, R.L. and Braunwald, E.: Studies on digitalis III. The influence of tri-iodothyronine on digitalis requirements. Circulation 23: 376 (1961).
Gallagher, T.F.; Hellman, L.; Finkelstein, J.: Yoshida, K.; Weitzman, E.D.; Roffwarg H.D. and Fukushima, D.K.: Hyperthyroidism and Cortisol secretion in man. Journal of Clinical Endocrinology and Metabolism 34: 919–927 (1972).
Gilfrich, H.J.: Untersuchungen zur Pharmakokinetik von Digoxin bei hyperthyreoten Patienten Verhandlungen der Deutschen Gesellschaft fur Innere Medizin 25, Wiesbaden (29 April 1976).
Gillette, J.R.: Drug toxicity as a result of interference with physiological control mechanisms. Annals of the New York Academy of Sciences 123: 42–54 (1965).
Gordon, G.G.; Sonthern, A.L.; Tochimoto, S.; Rand, J.J. and Olivo, J.: Effect of hyperthyroidism and hypothyroidism on the metabolism of testosterone and androstenedione in man. Journal of Clinical Endocrinology and Metabolism 29: 164–170 (1969).
Gugler, R.; Eichelbaum, M.; Schneider-Deters, Ch.; Bodem, G. and Dengler, H.J.: Einfluss der Schilddrüsenfunktion auf den Arzneimittelstoffwechsel beim Menschen. Verhandlungen der Deutschen Gesellschaft für Innere Medizin 79: 1230–1233 (1973).
Hartmann, C.R.; Klaassen, C.D. and Huffman, D.H.: The biliary excretion of digoxin and metabolites in hyperthyroid rats. Clinical Research 23: 220A (1975).
Kato, R. and Gillette, J.R.: Sex differences in the effect of abnormal physiological states on the metabolism of drugs by rat liver microsomes. Journal of Pharmacology and Experimental Therapeutics 150: 285–291 (1965).
Kampmann, J. and Skovsted, L.: The pharmacokinetics of propylthiouracil. Acta Pharmacologica et Toxicologica 35: 361–369 (1974).
Kampmann, J. and Skovsted, L.: The kinetics of propylthiouracil in hyperthyroidism. Acta Pharmacologica et Toxicologica 37: 201–210 (1975).
Kato, R. and Takahashi, A.: Thyroid hormone and activities of drug-metabolizing enzymes and electron transport systems of rat liver microsomes. Molecular Pharmacology 4: 109–120 (1968).
Kristensen, M.B.: Medikament-medikament interaktion Thesis, 1973, FADL, 92-96 loc. cit.: Kampmann and Skovsted (1975).
Levy, G.; MacGillivray, M.H. and Procknal, J.A.: Riboflavin absorption in children with thyroid disorders. Pediatrics 50: 896–900 (1972).
MacNee, C.; Headley, A.J.: Adamson, D.G. and Crooks, J.: Drug metabolizing capacity in thyroid disease. Israel Journal of Medical Science 8: 42–43 (1973).
Morrow, D.H.; Gaffney, T.E. and Braunwald, E.: Studies on digitalis VII. Influence of hyper- and hypothyroidism on the myocardial response to ouabain. Journal of Pharmacology and Experimental Therapeutics 140: 324 (1963).
O’Reilly, R.A. and Aggeler, P.M.: Determinants of the response to oral anticoagulant drugs in man. Pharmacological Reviews 22: 35–96 (1970).
Peacock, W.F. and Moran, N.C.: influence of thyroid state on positive inotropic effect of ouabain on isolated ventricle strips. Proceedings of the Society of Experimental Biology and Medicine 113: 526–530 (1963).
Peterson, R.E.: The influence of the thyroid on adrenal cortical function. Journal of Clinical Investigation 37: 736–743 (1958).
Prange, A.J. and Lipton, M.A.: Enhancement of imipra-mine mortality in hyperthyroid mice. Nature 196: 588–589 (1962).
Prange, A.J.; Lipton, M.A. and Love, G.N.: Effect of altered thyroid status on desmethylimipramine mortality in mice. Nature 204: 1205–1206 (1964).
Prange, A.J.; Lipton, M.A. Shearin, R.B. and Love, G.N.: The influence of thyroid status on the effects and metabolism of pentobarbital and thiopental. Biochemical Pharmacology 15: 237–248 (1966).
Ratcliff, C.R.; Gilliland, P.F. and Hall, F.F.: Serum propylthiouracil: Determination by a direct colorimetric procedure. Clinical Chemistry 18: 1373–1375 (1972).
Schuppan, D.; Riegelman, S.; Lehmann, B.; Pilbrandt, A. and Becker, C.: Preliminary pharmacokinetic studies of propylthiouracil in humans. Journal of Pharmacokinetics and Biopharmaceutics 1: 307–318 (1973).
Sitar, D.S. and Hunninghake, D.B.: Pharmacokinetics of propylthiouracil in man after a single oral dose. Journal of Clinical Endocrinology and Metabolism 40: 26–29 (1975).
Solomon, H.M. and Schrogie, J.J.: Change in receptor site affinity: a proposed explanation for the potentiating effect of D-thyroxine on the anticoagulant response to warfarin. Clinical Pharmacology and Therapeutics 8: 797–799 (1967).
Schrogie, J.J. and Solomon, H.M.: The anticoagulant response to bishydroxycoumarin II. The effect of D-thyroxin, clofibrate and norethandrolone. Clinical Pharmacology and Therapeutics 8: 70–77 (1967).
Thomas, F.B.; Caldwell, J.H. and Greenberger, N.J.: Steatorrhea in thyrotoxicosis Relation to hypermotility and excessive dietary fat. Annals of Internal Medicine 78: 669–675 (1973).
Vesell, E.S.; Shapiro, J.R.; Passananti, G.T.; Jorgensen, H. and Shively, C.A.: Altered plasma half-lives of antipyrine, propylthiouracil and methimazole in thyroid dysfunction. Clinical Pharmacology and Therapeutics 17: 48–56 (1975).
Wenckebach, K.F. and Winterberg, H.: Die unregelmässige Herztätigkeit, p.493 (Wilhelm Englemann, Leipzig 1927).
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Eichelbaum, M. Drug Metabolism in Thyroid Disease. Clin Pharmacokinet 1, 339–350 (1976). https://doi.org/10.2165/00003088-197601050-00002
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DOI: https://doi.org/10.2165/00003088-197601050-00002