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Type: Journal article
Title: The impact of thyroid disease on the regulation, expression, and function of ABCB1 (MDR1/P-glycoprotein) and consequences for the disposition of digoxin
Author: Burk, O.
Brenner, S.
Hofmann, U.
Tegude, H.
Igel, S.
Schwab, M.
Eichelbaum, M.
Alscher, M.
Citation: Clinical Pharmacology & Therapeutics, 2010; 88(5):685-694
Publisher: Mosby Inc
Issue Date: 2010
ISSN: 0009-9236
Statement of
O. Burk, S.S. Brenner, U. Hofmann, H. Tegude, S. Igel, M. Schwab, M. Eichelbaum and M.D. Alscher
Abstract: The impact of thyroid dysfunction on the regulation, expression, and function of ABCB1 remains unclear. We therefore investigated ABCB1 mRNA expression and function in patients with thyroid dysfunction and studied the disposition of the ABCB1 substrate digoxin before and after treatment for thyroid disease. In patients with hypothyroidism, normalization of thyroid function was associated with a 1.8-fold increase in mRNA expression and a 26% increase in rhodamine efflux from CD56+ cells. In hypothyroidism, digoxin clearance was significantly decreased, whereas bioavailability, volume of distribution, half-life time, and protein binding were unaltered. In hyperthyroidism, ABCB1 mRNA expression, rhodamine efflux, and disposition of digoxin were not significantly affected other than in relation to renal clearance. Experiments using the LS174T cell line indicated that the gene is a direct target of thyroid hormone receptors. In conclusion, thyroid abnormalities can exert significant effects on the expression of P-glycoprotein, thereby altering the disposition and action of drugs that are substrates of P-glycoprotein.
Keywords: Caco-2 Cells; Humans; Hyperthyroidism; Hypothyroidism; Rhodamines; Digoxin; Thyroid Hormones; P-Glycoprotein; RNA, Messenger; Cardiotonic Agents; Administration, Oral; Infusions, Intravenous; Transfection; Gene Expression Regulation; Adult; Aged; Middle Aged; Female; Male; Enhancer Elements, Genetic; Young Adult
Rights: © 2010 American Society for Clinical Pharmacology and Therapeutics
RMID: 0020102515
DOI: 10.1038/clpt.2010.176
Appears in Collections:Pharmacology publications

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