The Pharmacokinetics And Safety Evaluation Of Compound Butaphosphan Injection In Calves

Compound butaphos injection is composed of butaphos and vitamin B₁₂,which can be used as an effective body supplement for phosphorus-deficient animals and stressed animals,and has broad application prospects.At present,compound butaphos injection has been widely used abroad,but it has not been approved for use in target cattle in China,which limits the application of the product in the cattle industry.Therefore,in this study,compound butaphos injection was used as the test preparation,and the pharmacokinetic and safety tests in target cattle were completed,which provided a basis for later clinical treatment trials.In this study,a single dose,double cycle,two sequences,randomized,crossover,and controlled design was used to conduct a pharmacokinetic study of compound butaphosphan injection in healthy calves.A 7-day cleaning period was set during two weeks period.Six healthy calves were selected and randomly divided into two groups（three in each group）.The order of administration for one group of animals was intravenous first,followed by intramuscular injection;The order of administration for the other group was to administer the drug via intramuscular injection first,followed by intravenous administration.The intravenous route is jugular vein administration.The recommended dosage for both formulations is 12.5 ml per dose.Blood was collected through the jugular vein at different time points before and after administration,and the plasma content of butaphosphan was measured using LC-MS/MS method.The non-compartment model analysis method in the pharmacokinetic module of DAS 3.0 software was used to analyze the drug time data.After intravenous injection of compound butaphosphan injection into healthy calves,the main pharmacokinetic parameters were:the average retention time MRT（0-t）of intravenous injection was1.44±0.13h,the average peak concentration Cmax was 55024.88±17517.45ng/m L,and the area under the drug time curve AUC（0-t）was 38840.42±14325.63ng/m L·h.The mean retention time MRT（0-t）for intramuscular injection was 2.36±0.36 h,the peak time was 0.18±0.04 h,the mean peak concentration Cmax was 33840.18±16656.81 ng/m L,and the mean area under the drug time curve AUC（0-t）was 27511.42±9647.48 ng/m L·h.The above parameters indicate that the absorption rate of butaphosphan in cattle is faster,the peak time is shorter,and the average retention time in the blood is shorter.The elimination rate constants for intravenous and intramuscular injection were 0.23±0.17h-1 and 0.40±0.15h-1,respectively.The half-lives of intravenous and intramuscular injections were 5.59±4.58 hours and 2.19±1.53 hours,respectively.The bioavailability F was 70.83%.The results showed that after intramuscular injection of compound butaphosphan injection into calves,the absorption was rapid,the distribution was widespread,the elimination was slow,and the bioavailability was high.Therefore,the systemic effects of local administration on the body should be considered during clinical medication.This experiment further carried out the safety study of compound butaphosphan injection on target animal cattle.Sixteen healthy calves were selected and randomly divided into four groups,namely,a negative control group,one-time drug dose group（compound butafos injection,8 m L）,three times drug dose group（compound butafos injection,24 m L）,and five times drug dose group（compound butafos injection,40 m L）.After weaning,it is injected for three consecutive days,once a day.Clinical observation and scoring were conducted on calves in each group every day.Calf blood was collected for the detection of physiological and biochemical indicators,immune indicators,stress hormones,and antioxidant stress-related indicators.On the 3rd day,two calves in the control group and the 5-fold drug dose group were randomly selected for necropsy and histopathological examination,respectively.Then on the 10th day,the remaining calves in the control group and the 5-fold drug dose group were subjected to autopsy and histopathological examination.The results showed that 1,3,and 5-fold doses of compound butafos injection could effectively alleviate weaning stress in calves,and increase immunity and antioxidant capacity of calves.In contrast 1,3,and 5-fold doses of compound butafos injection did not affect physiological and biochemical indicators of calves.The results of autopsy and histopathology also showed that 5 times the drug dose of compound butafos injection did not cause histopathological damage to the principal organs of cattle in the target animal.This study conducted a pharmacokinetic study of compound butaphosphan injection in calves through plasma collection and sample analysis and evaluated its safety in calves.At the same time,the absorption and metabolism rules of compound butaphosphan in calves were analyzed,as well as the safety for target animals when used at this dose and double doses,reducing the risk of medication,and promoting the clinical use of compound butaphosphan injection in the cattle industry.