The Impact of Thyroid Disease on the Regulation, Expression, and Function of ABCB1 (MDR1/P Glycoprotein) and Consequences for the Disposition of Digoxin
| العنوان: | The Impact of Thyroid Disease on the Regulation, Expression, and Function of ABCB1 (MDR1/P Glycoprotein) and Consequences for the Disposition of Digoxin |
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| المؤلفون: | Stefanie Brenner, Oliver Burk, Matthias Schwab, Svitlana Igel, Michel Eichelbaum, Ute Hofmann, M D Alscher, Heike Tegude |
| المصدر: | Clinical Pharmacology & Therapeutics. 88:685-694 |
| بيانات النشر: | Springer Science and Business Media LLC, 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Adult, Male, Digoxin, Thyroid Hormones, endocrine system, medicine.medical_specialty, ATP Binding Cassette Transporter, Subfamily B, Cardiotonic Agents, endocrine system diseases, Administration, Oral, Pharmacology, Transfection, Hyperthyroidism, Young Adult, Hypothyroidism, Internal medicine, medicine, Humans, Pharmacology (medical), ATP Binding Cassette Transporter, Subfamily B, Member 1, RNA, Messenger, Infusions, Intravenous, Aged, P-glycoprotein, Volume of distribution, Thyroid hormone receptor, biology, Rhodamines, Chemistry, Thyroid disease, Middle Aged, medicine.disease, Enhancer Elements, Genetic, Endocrinology, Gene Expression Regulation, Cell culture, biology.protein, Female, Efflux, Caco-2 Cells, Thyroid function, medicine.drug |
| الوصف: | 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. Clinical Pharmacology & Therapeutics (2010) 88 5, 685–694. doi: 10.1038/clpt.2010.176 |
| تدمد: | 1532-6535 0009-9236 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::979e84aee1420ec2c9457a4d22b14c2cTest https://doi.org/10.1038/clpt.2010.176Test |
| رقم الانضمام: | edsair.doi.dedup.....979e84aee1420ec2c9457a4d22b14c2c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15326535 00099236 |
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