Session: SUN 414-431-HPT Axis Biology
Poster Board SUN-420
Purpose: We hypothesize that T4 transporting proteins expressed in the gut are the mechanistic site for inhibition of thyroid hormone absorption by concomitantly administered drugs. Thus, the goal of this study was to formally determine the acute effect of co-administration of ciprofloxacin on T4 absorption and compare that with a well-known OATP inhibitor (rifampin) to better elucidate the potential relevance of intestinal transporters to T4 absorption.
Methods: The effects of that two antibiotics on T4 absorption were prospectively assessed in double blind-randomized, crossover fashion. Eight healthy volunteers received 1000 microgram T4 combined with placebo, ciprofloxacin 750 mg or rifampin 600 mg as single doses. We measured total plasma T4 concentrations over a 6 hour period after dosing using liquid chromatography-tandem mass spectrometry (LC-MS/MS). For each study arm, T4 areas under the plasma concentration-time curve (AUC) were compared.
Results: Co-administration 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 T4 is differentially affected by acute co-administration of ciprofloxacin or rifampin. Mechanistic studies focused on intestinal, and possibly hepatic thyroid hormone transporters are required to explain the observed drug interactions with T4.
Nothing to Disclose: AG, RT, LA, RK, SV
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