The Studies On The Rompun Combination Of Anaesthetic For Goats And The Pharmacokinetics Of Rumpun

The experiment was based on balanced anesthesia theory and according to mechanism of action of different drugs, binding sites, anesthetic effects and physiological characteristics of goats to determine the components of combined anesthetic and their proportion by preliminary test, orthogonal experiment and orthogonal decisive test. The security of combined anesthetic was evaluated by drug safety experiment, and then the effect was estimated after monitoring the physiological indexes in order to provide a safety and reliable combined anesthetic for goats. Metabolic regularity of Rompun was researched by HPLC in goats.The components of combined anesthetic were determined to be Rompun, Midazolam, Qiangtongning by preliminary test. The best proportion, 0.3:0.2:0.07(calculated by the single injection in composition), was determined by orthogonal test and orthogonal decisive test and the safety factor was 4.41 which was determined by ED50 and LD50 tests. Above all, the safety margin of the combined anesthetic was consistent with clinical request and called it Rompun combinantion.The physiological indexes and the change of biological reflection were monitored after intramuscular injection in different phases by 0.3mL/kg with Rompun combinantion in goats and then the datum were needed to be analyzed. The feasibility of Rompun combinantion in clinical application was evaluated. The results showed that: the anaesthetic effects of Rompun combinantion were reliable and effects of analgesia, sedation, muscle relaxation were better, there is no significant change of physiological indexes in anesthetic stage; all the indexes were in normal extent and the combined anesthetic could satisfied the request of clinical application. The concentration of Rompun in plasma of goats was determined by the method which was qualitation and quantitation established with HPLC-UV and the feather of Rompun pharmacokinetics was researched. The appearance time of Rompun chromatographic peak is 9-11min; when the concentration of Rompun was 10^-1000ng, linear correlation coefficient of standard curve R2=0.9982; sample recovery rate was 91.2%⁹5.7% and the largest variation coefficient was 11.1%; the lowest detectable limit was 3ng and the lowest quantitation limit was 10ng of which were below the largest concentrations of 1/20 so that satisfied the request of experiment design.The pharmacokinetics model of Rompun was first order kinetics single compartment model, the theory equations of it was D(t)=572.76×(e-0.03t– e^-1.43t);Absorption rate constant, Ka=1.43±0.12min^-1, Clearance rate constant, Ke=0.030±0.0017min^-1; Distribution half-life, t1/2Ka=0.49±0.041min; Elimination half-life, t1/2Ke=23.3±2.5min; Peak time of maximum concentration, Tp=2.8±0.2min; total clearance of drug, CL/F=0.00016±0.000016mg/kg/min/(ng/ml). The lowest effective blood drug concentration was 56.6ng/mL. All the above showed that the absorption of Rompun was quickly, the distribution was generally; the time reached the peak was short; the rate of eliminate was slow and the duration was long.The results showed that, the effects of the combined anesthetic were stable, the influence to physiological indexes were slight and the safety margin was wide so that it can satisfy the request of clinic anesthesia; the method of monitoring Rompun pharmacokinetics was reliable and applicable; Rompun was absorbed fast, distributed widely and maintenance time was long in goats.