HPLC determination and pharmacokinetics of thiabendazole and its major metabolite 5-OH thiabendazole in equine plasma.

This research presents a method of determining and understanding the pharmacokinetics of a drug, Thiabendazole and its major metabolite, 5-OH Thiabendazole, in horse plasma.

Methodology

• The researchers created high performance liquid chromatographic methods to determine the levels of thiabendazole (TBZ) and 5-hydroxy thiabendazole (5-OH-TBZ) in horse plasma.
• 1-Methyl-2-phenyl benzimidazole (MPBZ) was used as an internal standard in both established methods.
• To separate TBZ and 5-OH-TBZ from the plasma, they used organic solvents and injected the extracted elements on to a C-18 column.
• Eluents were monitored by a fluorescence detector. Notwithstanding, the detector wavelength, extraction solvent and mobile phase composition differed in the two methods designed.
• Linear range for TBZ was 0.02 to 0.77 microgram ml-1 and that for 5-OH-TBZ was 0.96 to 8.0 micrograms ml-1.

Experimentation and Results

• A TBZ oral suspension, commercially available, was administered to four thoroughbred horses for four days in two differing dose regiments: 44 mg kg-1 on days 1 and 2, and 440 mg kg-1 on days 4 and 5.
• Blood samples were collected in the 24 hours post the administration and were analysed for TBZ and 5-OH-TBZ.
• Half-lives (t1/2), maximum plasma concentrations (Cmax), area under plasma concentration time curves (AUC O-alpha), and relative apparent bioavailability (F), were determined using pharmacokinetic equations.
• They noticed that the pharmacokinetic parameters varied in this range: 1.16 to 13.63 hours (t1/2), 12 to 131 micrograms ml-1 X hours (AUC O-alpha), 3.33 to 8.90 micrograms ml-1 (Cmax), 1.38 to 0.12 (F) after 44 mg kg-1 and 440 mg kg-1 doses.
• The ratios of the concentrations of TBZ to 5-OH-TBZ following oral administration of TBZ was found to be significantly lower for 44 mg kg-1 than 440 mg kg-1 doses.