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).

Conclusion:

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.