The Comparative Pharmacokinetic Of Two Altrenogest Oral Solution In Sows

Altrenogest is a synthetic progesterone that is clinically used mainly in the synchronization of estrus between sows and mares.Altrenogest absorbs quickly in animals,has short peak time,and has high bioavailability.However,altrenogest is low in toxicity and has less residue in the edible tissues of animals.In this study,the pharmacokinetics parameters such as relative bioavailability were obtained by comparing the pharmacokinetics of domestically produced altrenogest oral solution with imported similar drugs.This study not only has important guiding significance for drug prescription screening and preparation process evaluation,but also the relevant pharmacokinetic parameters have important reference value for predicting the duration of drug withdrawal and rational drug use of altrenogest in food animals.1.A method for the Determination of Altrenogest in Porcine Plasma by UPLC-MS/MSAltrenogest in plasma was extracted by liquid-liquid extraction method,using Inertsil C4(3 x 150 mm,5 m)column and gradient elution,multiple reaction monitoring three level four pole mass spectrometer(MRM)model for quantitative analysis,internal standard method.The mobile phase A was 5 mM ammonium formate solution,B was acetonitrile,the flow rate was 0.4 ml/min,the sample size was 10 μL.In this method has a good linear relationship in the concentration range of 1 ng/mL～100 ng/mL,and the correlation coefficient was greater than 0.999 2.The inter-assay recoveries of altrenogest at low,medium,and high concentrations(1 ng/mL,50 ng/mL,and 100 ng/mL)blank plasma samples were 93.1%±3.98%,92.7%± 5.75%,88.9%±3.69%,the coefficient of intra-day variation were 3.50%～14.35%,3.43%～6.20%and 2.88%～4.15%,the coefficient of variation between days was between 5.11%～8.86%.The method has a limit of detection(LOD)of 0.5 ng/mL and a limit of quantitation(LOQ)of 1 ng/mL.Matrix effect enhanced the determination of altrenogest,which was 114.65%at low concentrations(1 ng/mL),109.23%at medium concentrations(50 ng/mL),and high concentrations(100 ng/mL)was 113.59%..After the treated sample was placed in the sample room(4℃)for 8 hours,the coefficient of variation at the three levels of low,medium,and high concentrations was less than 11%,indicating that altrenogest has higher stability present in the sample chamber during the measurement time.After the sample to be tested was thawed and thawed three times,the coefficient of variation of the three levels of low,medium and high concentrations was less than 9%,indicating that after 3 cycles of freeze-thawing,the altrenogest in the plasma sample was still highly stable.The method can be used for the accurate determination of the content of altrenogest in porcine plasma.2.The Comparative Pharmacokinetic of Two Altrenogest Oral Solution in SowsUsing cross-experiment design,8 sows with similar body weight were randomly divided into two groups with 4 pigs in each group.In the first stage,the first group of 4 sows were orally administered with altrenogest oral solution of test products and the second group of 4 sows were orally administered with altrenogest oral solution of reference products;In the second stage,the first group of 4 sows were orally administered with the altrenogest oral solution of reference product,and the second group of 4 sows was orally administered with altrenogest oral solution of test product.The two-phase elution time is 1 week,.Fasting was performed for 12 hours prior to administration and a blank blood sample was collected.The content of altrenogest in plasma was determined by validated UPLC-MS/MS.The measured plasma concentration-time data was fitted with pharmacokinetic parameters using Winnonlin 5.2 pharmacokinetic analysis software.After the single oral dose of oral altrenogest oral solution of the test and reference product the average elimination half-life(ti/2)was 6.44 h and 6.43 h,and the peak time(Tmax)was 0.84 h and 1.09 h,the peak concentrations(Cmax)were 55.41 ng/mL and 57.39 ng/mL,the clearance rates(Cl)were 2781.02 mL/h/kg and 3727.67 mL/h/kg,the apparent volume of distribution(Vd)was 24924.69 mL/kg and 36418.91 mL/kg,the average residence time(MRT0-t)were 6.36 h and 6.79 h,and the area under the average drug-time curve(AUC0-t)was 424.37 h*ng/mL and 311.68 h*ng/mL,respectively.The results showed that the oral absorption and elimination of altrenogest oral solution in sows were rapid.Compared with the reference products,the relative bioavailability of the test products was 136.29%,and the degree of absorption was better than that of imported similar products.There was no significant difference in the main pharmacokinetic parameters t1/2,Tmax,Cmax,Cl,Vd,AUC0～t,AUC0～∝,and MRT0～t between the test group and the reference group(P>0.05).The results showed that there were similar pharmacokinetic characteristics between the products of the test products and the reference products.