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

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. 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. 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. 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.

Citation

Werner Siegmund, Stephan Altmannsberger, Andrea Paneitz, Ute Hecker, Michael Zschiesche, Gerd Franke, Wieland Meng, Rolf Warzok, Eike Schroeder, Bernhard Sperker, Bernd Terhaag, Ingolf Cascorbi, Heyo K Kroemer. Effect of levothyroxine administration on intestinal P-glycoprotein expression: consequences for drug disposition. Clinical pharmacology and therapeutics. 2002 Sep;72(3):256-64

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PMID: 12235446

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