title: Effect of levothyroxine administration on intestinal P-glycoprotein expression: consequences for drug disposition.
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.
authors.affiliation: Department of Clinical Pharmacology, Peter Holtz Research Center of Pharmacology and Experimental Therapeutics, University of Greifswald, Greifswald, Germany. siegmuw@uni-greifswald.de
authors.forename: Werner
authors.initials: W
authors.lastname: Siegmund
authors.forename: Stephan
authors.initials: S
authors.lastname: Altmannsberger
authors.forename: Andrea
authors.initials: A
authors.lastname: Paneitz
authors.forename: Ute
authors.initials: U
authors.lastname: Hecker
authors.forename: Michael
authors.initials: M
authors.lastname: Zschiesche
authors.forename: Gerd
authors.initials: G
authors.lastname: Franke
authors.forename: Wieland
authors.initials: W
authors.lastname: Meng
authors.forename: Rolf
authors.initials: R
authors.lastname: Warzok
authors.forename: Eike
authors.initials: E
authors.lastname: Schroeder
authors.forename: Bernhard
authors.initials: B
authors.lastname: Sperker
authors.forename: Bernd
authors.initials: B
authors.lastname: Terhaag
authors.forename: Ingolf
authors.initials: I
authors.lastname: Cascorbi
authors.forename: Heyo K
authors.initials: HK
authors.lastname: Kroemer
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000235:genetics; D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics; D000328:Adult; D019540:Area Under Curve; D004386:Duodenum / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D019450:Genes, MDR / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D004364:Pharmaceutical Preparations / Q000378:metabolism; D011412:Propanolamines / Q000008:administration & dosage / Q000493:pharmacokinetics; D012333:RNA, Messenger / Q000096:biosynthesis; D018709:Statistics, Nonparametric; D013974:Thyroxine / Q000008:administration & dosage*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000319:Adrenergic beta-Antagonists; D004364:Pharmaceutical Preparations; D011412:Propanolamines; D012333:RNA, Messenger; C011550:talinolol; D013974:Thyroxine