PHARMACOKINETICS OF NITAZOXANIDE AFTER SINGLE ORAL DOSE ADMINISTRATION IN 6 HEALTHY-VOLUNTEERS

The objective of this study was to gather first information on the tim e course of plasma concentrations and urinary excretion of the antipro tozoal nitazoxanide (N) and to identify potential metabolites in healt hy subjects after a single oral dose of 500 mg of nitazoxanide. The cl inical trial was conducted as an open single oral dose study in 6 heal thy male subjects. After a standardized continental breakfast the subj ects took a single oral dose of 500 mg nitazoxanide (coated tablet) wi th 100 ml tap water. The plasma concentration and the urinary excretio n of nitazoxanide (N), desacetyl-nitazoxanide (DN), aminonitrothiazole (ANT), acetylsalicylate (AS), salicylate (S), gentisate (G) and salic ylurate (SU) were monitored up to 72 h after administration. The only measurable species in plasma was DN, which reached a C-max of 1.9 mg/l (range 1.1-2.5) 2-6 h after dosing, and an AUC of 3.9-11.3 mg x h/l. Its terminal half-life ranged from 1.03 to 1.6 h. DN was extensively b ound to plasma proteins (>97.5%). Only 8% of the dose was recovered in the urine, in the form of DN (5%), SU (3%), and traces of ANT (0.1%). In vitro N was very rapidly hydrolyzed to DN by plasma esterases.