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Clin Pharmacol Ther. 2002 Sep;72(3):256-64.

Effect of levothyroxine administration on intestinal P-glycoprotein expression: consequences for drug disposition.

Author information

1
Department of Clinical Pharmacology, Peter Holtz Research Center of Pharmacology and Experimental Therapeutics, University of Greifswald, Greifswald, Germany. siegmuw@uni-greifswald.de

Abstract

OBJECTIVE:

Thyroid function alters the pharmacokinetics of many drugs; one example is the cardiac glycoside digoxin. Because digoxin disposition is affected by intestinal expression of P-glycoprotein, we hypothesized that thyroid hormones may regulate P-glycoprotein and influence disposition of P-glycoprotein substrates.

METHODS:

Duodenal expression of P-glycoprotein measured by reverse transcriptase-polymerase chain reaction of MDR1 messenger ribonucleic acid (mRNA) and by immunohistochemical examination was studied in 8 healthy volunteers (4 men and 4 women; age range, 22-29 years; body weight, 59-89 kg) before and after coadministration with levothyroxine (200 microg orally for 17 days), which resulted in suppression of thyroid-stimulating hormone. The pharmacokinetics of the P-glycoprotein substrate talinolol was assessed after intravenous (30 mg) and oral (100 mg) administration.

RESULTS:

Duodenal MDR1 mRNA expression and immunoreactive P-glycoprotein were increased 1.4-fold (not significant; P =.078) and 3.8-fold (P <.01), respectively, after administration of levothyroxine. The changes in P-glycoprotein expression were associated with minor alterations in talinolol half-life after both oral and intravenous administration.

CONCLUSIONS:

Expression of intestinal P-glycoprotein in humans appears to be influenced by thyroid hormones. The functional consequences need to be addressed in patients with hyperthyroidism.

PMID:
12235446
DOI:
10.1067/mcp.2002.126706
[Indexed for MEDLINE]

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