Pharmacokinetics Of Dry Suspension Of Nitazoxanide In Dogs

Nitazoxanide (NTZ) was an interesting parasiticides,fungistatic and molluscicidal agent. As a new broad spectrum antiparasitic agent. Presently , there are no reports on the pharmacokinetics of this drug in dogs inside or outside our country. We processed this study aiming to find out the drug's changing rule and offer theory for new drug design and clinic experimentations.We refined tizoxanide and worked out its content is 99.4% with area normalization method. By analyzing the HPLC chromatogram and mass spectrum, we fixed on the condition:add 20μl pH4.3 buffer, 2μlβ-glucuronidase to 0.2ml plasma, 37℃constant temperature staying over.Tizoxanide is the main activity metabolize of nitazoxanide in dog plasma, and then, it combine with glucuronides becoming tizoxanide glucuronide. In this study, we developed a strategy for identification of nitazoxanide's phase II conjugate using neutral loss scans on a triple quadrupole mass spectrometer successfully.A RP-HPLC method for the determination of tizoxanide the major metabolite of nitazoxanide in dog's plasma was developed for pharmacokinetic research. Methods: The major metabolite was determined on a Scienhome Kromasil C-(18) column (250×4.6mm,5μim) using acetonitrile-0.02mol/l(pH2.5) phosphate buffer(50:50) as mobile phase at a flow rate of 1 .Oml/min, and detected at 360nm. Result: The linear relationship of the peak area and concentration was determined as 0.1 12.5μg/ml by RP-HPLC, with a regression coefficient of 0.9996(n=5). The limit of detection was 0.02 μg/ml. Conclusions: The method is simple, rapid and accurate, it can be used in pharmacokinetic studies.The pharmacokinetics of the main activity metabolin of dry suspension of Nitazoxanide was studied in dogs. Methods: Following administration of a single dose of 50, 100 and 200mg/kg dry suspension of Nitazoxanide to dogs, blood drug concentrations were determined by HPLC. Then the pharmacokinetic parameters were calculated. Results: The pharmacokinetic process of the main metabolite of dry suspension of Nitazoxanide in dogs fitted to one compartment open model. At 50, 100, and 200 mg/kg doses, the respective C_max were 0.60±0.12, 1.01±0.11, 2.11±0.27μg/ml; respective t_1/2ke were 3.18±0.25, 3.35±0.64, 3.32±0.55h; respective AUC were 5.34±0.80, 11.71±2.91, 24.30±2.86μgh/ml.The pharmacokinetics of metabolites of dry suspension of Nitazoxanide was studied in dogs. Methods: Following administration of a single dose of 50, 100 and 200mg/kg dry suspension of Nitazoxanide to dogs, blood drug concentrations were determined by HPLC...