title: The pharmacokinetics of nitazoxanide active metabolite (tizoxanide) in goats and its protein binding ability in vitro.
abstract: 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.
authors.affiliation: Department of Pharmacy, Key Laboratory for Veterinary Drug Safety Evaluation and Residue Research, Chinese Academy of Agricultural Sciences, Shanghai, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhao
authors.forename: F
authors.initials: F
authors.lastname: Xue
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: K
authors.initials: K
authors.lastname: Zhang
authors.forename: C
authors.initials: C
authors.lastname: Fei
authors.forename: W
authors.initials: W
authors.lastname: Zheng
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Wang
authors.forename: Z
authors.initials: Z
authors.lastname: Zhao
authors.forename: X
authors.initials: X
authors.lastname: Meng
mesh_terms: D000818:Animals; D000977:Antiparasitic Agents / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D001798:Blood Proteins / Q000378:metabolism*; D006041:Goats / Q000378:metabolism*; D008297:Male; D009574:Nitro Compounds; D011485:Protein Binding; D013844:Thiazoles / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*
chemical_list: D000977:Antiparasitic Agents; D001798:Blood Proteins; D009574:Nitro Compounds; D013844:Thiazoles; C104067:tizoxanide; C041747:nitazoxanide