Effects of nitazoxanide on pharmacokinetics and pharmacodynamics of a single dose of warfarin.
OBJECTIVE
The effects of nitazoxanide on warfarin pharmacokinetics and pharmacodynamics are examined.


METHODS
This was a Phase I, single-center, open-label, randomized, two-way, crossover study. Secondary endpoints included an evaluation of the effect of nitazoxanide on coagulation parameters observed after a single dose of warfarin and an assessment of the overall tolerability of study treatments. Fourteen healthy men were selected for the study. The study consisted of two treatment periods (Treatment A and Treatment B), each lasting 6 days, with a washout period of at least 21 days between both warfarin intakes. All subjects were scheduled to receive both Treatment A and Treatment B, according to the randomization list. Treatment A consisted of a single oral dose of 25 mg warfarin sodium (five 5-mg tablets). Treatment B consisted of a single oral intake of 25 mg warfarin sodium (five 5-mg tablets) and one 500-mg tablet of nitazoxanide (with nitazoxanide 500 mg continued twice daily for up to 6 days).


RESULTS
All 14 subjects received Treatment B, and 13 of the 14 subjects received Treatment A. Pharmacokinetic results were similar in both treatments, and pharmacodynamic parameters were similar in both treatments. Fourteen adverse events occurred in eight subjects after administration of at least one dose of the study drug. Eleven adverse events occurred in six subjects after treatment with warfarin and nitazoxanide, and three adverse events occurred in two subjects after treatment with warfarin alone. At discharge, a high hemoglobin level and a low total bilirubin level were reported in both groups.


CONCLUSIONS
Coadministration of nitazoxanide twice daily for six days did not affect the pharmacokinetic or pharmacodynamic properties of a single 25-mg dose of warfarin sodium. Administration of a single dose of warfarin or combined administration of a single dose of warfarin and multiple doses of nitazoxanide appeared safe and well tolerated.
Vets
Eva
E
SGS Biopharma Research Unit, Stuivenbert, Antwerp, Belgium.
Rossignol
Jean-Francois
JF
Jackson
Anthony Shane
AS
D000293:Adolescent; D000328:Adult; D000977:Antiparasitic Agents / Q000008:administration & dosage / Q000009:adverse effects; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D004347:Drug Interactions / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009574:Nitro Compounds; D013844:Thiazoles / Q000008:administration & dosage* / Q000009:adverse effects; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*
D000977:Antiparasitic Agents; D009574:Nitro Compounds; D013844:Thiazoles; D014859:Warfarin; C041747:nitazoxanide