The goal of the in vitro research was to evaluate the potential for inhibition of warfarin protein binding by tizoxanide. Warfarin was of particular interest for the present investigation because it has been shown to be highly bound to plasma proteins and is a narrow therapeutic index drug. Tizoxanide is an active metabolite of an anti-infective prodrug nitazoxanide and also highly protein-bound medication. Both drugs are expected to be co-administered clinically. Protein binding of warfarin was investigated using a centrifugal ultrafiltration technique. Co-administration of tizoxanide significantly inhibited protein binding of warfarin for all concentrations tested. Tizoxanide increased free fraction (fu) of warfarin 34, 28, and 20-fold for concentration of 50, 75, and 100 μg/ml, respectively. The interaction could potentially result in increasing the toxicity of warfarin therapy and the risk of bleeding.
Mullokandov, E., Ahn, J., Szalkiewicz, A., & Babayeva, M. (2014). Protein binding drug-drug interaction between warfarin and tizoxanide in human plasma. Austin Journal of Pharmacolology and Therapeutics, 2(7) [Article id1038].