The pharmacokinetics of nitazoxanide active metabolite (tizoxanide) in goats and its protein binding ability in vitro.

The pharmacokinetics of tizoxanide (T), the active metabolite of nitazoxanide (NTZ), and its protein binding ability in goat plasma and in the solutions of albumin and alpha-1-acid-glycoprotein were investigated. The plasma and protein binding samples were analyzed using a high-performance liquid chromatography (HPLC) assay with UV detection at 360 nm. The plasma concentration of T was detectable in goats up to 24 h. Plasma concentrations vs. time data of T after 200 mg/kg oral administration of NTZ in goats were adequately described by one-compartment open model with first order absorption. As to free T, the values of t(1/2Ka), t(1/2Ke), T(max), C(max), AUC, V/F((c)), and Cl((s)) were 2.51 +/- 0.41 h, 3.47 +/- 0.32 h, 4.90 +/- 0.13 h, 2.56 +/- 0.25 microg/mL, 27.40 +/- 1.54 (microg/mL) x h, 30.17 +/- 2.17 L/kg, and 7.34 +/- 1.21 L/(kg x h), respectively. After beta-glucuronidase hydrolysis to obtain total T, t(1/2ke), C(max), T(max), AUC increased, while the V/F((c)) and Cl((s)) decreased. Study of the protein binding ability showed that T with 4 microg/mL concentration in goat plasma and in the albumin solution achieved a protein binding percentage of more than 95%, while in the solution of alpha-1-acid-glycoprotein, the percentage was only about 49%. This result suggested that T might have much more potent binding ability with albumin than with alpha-1-acid-glycoprotein, resulting from its acidic property.