title: Ciprofloxacin and rifampin have opposite effects on levothyroxine absorption.
abstract: BACKGROUND
  Levothyroxine (L-T4) absorption varies between individuals, and can be affected by various concomitantly administered drugs. Case reports have indicated an association between cotreatment with ciprofloxacin or rifampin and hypothyroidism in patients on a stable L-T4 dose.
  
  
  METHODS
  The effects of two antibiotics on T4 absorption were prospectively assessed in a double-blind, randomized, crossover fashion. Eight healthy volunteers received 1000 μg L-T4 combined with placebo, ciprofloxacin 750 mg, or rifampin 600 mg as single doses. We measured total plasma thyroxine (T4) concentrations over a 6-hour period after dosing using liquid chromatography-tandem mass spectrometry. For each study arm, areas under the T4 plasma concentration-time curve (T4 AUCs) were compared.
  
  
  RESULTS
  Coadministration of ciprofloxacin significantly decreased the T4 AUC by 39% (p = 0.035), while, surprisingly, rifampin significantly increased T4 AUC by 25% (p = 0.003).
  
  
  CONCLUSIONS
  Intestinal absorption of L-T4 is differentially affected by acute coadministration of ciprofloxacin or rifampin. Mechanistic studies focused on intestinal and possibly hepatic thyroid hormone transporters are required to explain the observed drug interactions with L-T4.
authors: 1 Division of Endocrinology and Metabolism, Department of Medicine, Schulich School of Medicine and Dentistry, Western University , London, Canada .
authors: Alyse S
authors: AS
authors: Goldberg
authors: Rommel G
authors: RG
authors: Tirona
authors: Linda J
authors: LJ
authors: Asher
authors: Richard B
authors: RB
authors: Kim
authors: Stan H M
authors: SH
authors: Van Uum
mesh_terms: D000042:Absorption; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D002939:Ciprofloxacin / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000139:chemically induced*; D007408:Intestinal Absorption / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D008297:Male; D011446:Prospective Studies; D012293:Rifampin / Q000494:pharmacology*; D013963:Thyroid Hormones / Q000378:metabolism; D013974:Thyroxine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013997:Time Factors; D055815:Young Adult
chemical_list: D013963:Thyroid Hormones; D002939:Ciprofloxacin; D013974:Thyroxine; D012293:Rifampin