Study On The Safety Evaluation, Stability And Pharmacokinetics In Swine Of The Novel Injection Of Compound Florfenicol

The novel injection of compound florfenicol with excellent clinical effect and low resistancecan be used in swine and cattle for respiratory disease. It is cmposed of special antibacterial drugflorfenicol, an anti-inflammatory drug flunixin meglumine and the suitable solvent. The injection’ssafety, the content determination methods of florfenicol and flunixin meglumine, stability test andpharmacokinetics in swine were carried out in this dissertation.1. The safety evaluation of the novel injection of compound florfenicol included pyrogen test,the LD50determination by intraperitoneal injection, skin and muscle irritation tests. The resultsshowed that the pyrogen test of the preparation was conformed to the provisions of Chineseveterinary Pharmacopoeia. LD50was1888.73mg·kg-1and the95%confidence limit was1575.90mg·kg-1～2263.65mg·kg-1. The injection had mild irritation to skin and slight irritation tomuscle, but it can recover absolutely after7days. All the results suggested that novel compoundflorfenicol injection was safe.2. The content determination methods of florfenicol (FF) and flunixin meglumine (FM) in thenovel injection of compound florfenicol were established by high performance liquidchromatography (HPLC). Hypersil ODS2column (5μm,4.6mm×250mm) was used. A mobilephase composed of acetonitrile and0.05%phosphoric acid (25:75, v/v) at a flow rate of1.0mL·min-1. The ultraviolet detector was set at224nm and column temperature was30℃. Thecontent of FF in five lots novel compound injection was98%～100%of labeled amount. The HPLCcondition of FM was as followed. Hypersil ODS2column (5μm,4.6mm×250mm) was used; amobile phase was composed of methanol and0.1%phosphoric acid (80:20, v/v) at a flow rate of1.0mL·min-1and the ultraviolet detector was set at254nm with30℃column temperature. Thecontent of FM in five lots novel compound injection was100%~103%of labeled amount. Themethods with accuracy, reliability, improved selectivity, and convenience could be employed todetermine the content of FF and FM in this novel compound florfenicol injection.3. The stability tests of novel compound florfenicol injection included high temperature test,high humidity test, strong illumination test and accelerated test. The results showed that the contentsof FF and FM did not have significant changes among the tests. The rubber plug could be used inthe preparation because of no obvious effect on the content change whether the samples wereupright, upside down or flat place. So the preparation is conformed to store and transport.4. The content determination methods of FF and FM in swine’s plasma were established. Thepharmacokinetics of novel compound florfenicol injection in swine were investigated. The resultssuggested that two methods were accurate, reliable, selective, convenient, and could be employed to determine the content of FF and FM in swine’s plasma. The drug concentration’s data in swine’splasma were analyzed by WinNonlin5.2pharmacokinetics software. The pharmacokineticparameters of FF in swine were as followed: Tmax2.09±0.59h; Cmax8.42±1.85μg·mL-1; CL203.75±31.39mL·h-1; AUC200.09±28.80h·μg·mL-1. The pharmacokinetics of FF in swine werefitted to one compartment model. FF of this injection was absorbed quickly and eliminated slowlyin swine with a longer time to reach Cmax, and could be maintained in a longer time with effectiveplasma concentration in swine.The pharmacokinetics parameters of FM in swine were as followed: Tmax0.60±0.21h; Cmax3.97±0.62μg·mL-1; T α0.82±0.38h; T β10.55±7.15h; AUC12.63±1.98h·μg·mL-1; α0.990.40h-1;β0.080.03h-1; CL294.29±40.49mL·h-1; Vdss1438.09±710.67mL. The pharmacokinetics of FM inswine were fitted to two compartments model. The pharmacokinetics parameters indicated that FMwas quickly absorbed and slowly eliminated with a shorter time to reach Cmaxand a longerelimination half life time.