Pharmacokinetics And Bioavailability Of Ponazuril Suspension In Piglets

Ponazuril is the main active metabolite of toltrazuril,which not only has anticoccidial activity,but also shows good activity against protozoa such as Neospora,Toxoplasma,Flagellate.Panazuril has been developed to treat equine encephalomyelitis(EPM).However,so far no reports have been approved for use in other animals.At present,there are few kinds of drugs that can be used for the prevention and control of piget coccidiosis.Therefore,the anticoccidial activity of ponazuril is expected to be developed for the prevention of piget coccidiosis.Through the study of the pharmacokinetic and bioavailability of Ponazuril Suspension in piglets,we are committed to providing a reasonable basis for the prevention of coccidiosis in piglets..1.Determination of ponazuril in piglet plasma by HPLCAn HPLC method for the determination of ponazuril in piglet plasma was established in this study.Ponazuril in piglet plasma was extracted and purified by liquid-liquid extraction with ethyl acetate,and separated by a C18 reverse chromatography column.The detector was a high-performance liquid chromatography ultraviolet detector,the detection wavelength was 250nm.Quantitative analysis was performed by external standard method.The mobile phase was acetonitrile-0.2%acetic acid aqueous solution(volume ratio 53:47),the flow rate was 1mL/min and the column temperature was 35℃.Ponazuril showed a good linear relationship in the concentration range of 0.10～10.00 μg/mL(R>0.999).The detection limit and quantitation limit of the method were 0.04 μg/mL and 0.1μg/mL.The intra-assay and inter-assay recovery rate were greater than 90%.The intra-assay and inter-assay precision coefficients of variation were less than 5%and 9%.This study established a method for purification and determination of ponazuril in piglet plasma,which is applicable to the determination of ponazuril in piglet plasma.2.Study on pharmacokinetics and bioavailability of Ponazuril Suspension in pigletsThis study used a parallel experimental design.Sixteen healthy 40-day-old piglets were randomLy divided into two groups,each with eight heads(half male and half female),given a single dose of intravenous injection(6 mg/kg bw)or a single dose of oral administration(15 mg/kg bw).All piglets were fasted for 12 hours before administration,and returned to normal diet after 2 hours of administration.Blood samples were collected at predetermined blood collection points after administration and were determined a validated HPLC detection method.The measured data used Graphad prism 8.0 to fit the drug time curve,and Winnonlin 5.2 was used to calculate the pharmacokinetic parameters.The main pharmacokinetic parameters of ponazuril in piglets after single-dose intravenous injection of ponazuril injection are as follows:the average elimination half-life(T1/2β)was 136.98h,the average residence time(MRT)was 165.92h,the area under the average drug time curve(AUCO-t)was 1577.97 h·μg/mL,the mean apparent volume of distribution(Vz)was 695.59 mL/kg and the mean plasma clearance(CL)was 3.77 mL/h·kg.The main pharmacokinetic parameters of ponazuril in piglets after single-dose oral ponazuril suspension are as follows:the average elimination half-life(T1/2β)was 134.05h,the average peak time(Tmax)was 42.00h,the average peak concentration(Cmax)was 14.03μg/mL,the average retention time(MRT)was 173.19 h and the area under the average drug time curve(AUCO-t)was 2831.00 h·μg/mL,the absolute bioavailability of ponazuril suspension was 72.08%.The results showed that ponazuril was poorly distributed in piglets,and was eliminated slowly.After oral administration of ponazuril suspension,it was well absorbed in piglets and the elimination time was slow.