The Content Determination, Safety Evaluation And Pharmacokinetic Studies Of Compound Florfenicol Injection

Compound Florfenicol Injection was a new preparation for curing calf pneumonia. The injection is composed of florfenicol, meloxicam, and other major active ingredients. In this study, composition of the compound florfenicol injection was further optimized, and determination of the injection, security assessment, pharmacokinetics in rabbits and calfs were carried out. These provide thesis basis for reasonable appplication and further pharmacodynamic evaluation of the injection.1. A HPLC method for the determination of florfenicol and meloxicam in compound florfenicol injection was established. The mobile phase was composed of methanol-water (40:60, adjusting pH to 3.0 with phosphoric acid) and the flow rate was 1ml?min^-1. Florfenicol and meloxicam samples were measured with UV detector at 222nm and 355nm. The retention time of florfenicol and meloxicam was 6.650min, 21.387min. The results showed that the content of florfenicol and meloxicam reached 97%, 98% of the labeled quantity.?The method is simple, rapid and sensitive with good repeatability, which can be used for content determination of compound florfenicol injection.2. The size of the injection of irritating is detected by muscle stimulation test and eye stimulation test. Four rabbits waere used to do irritating test, their weight is about 2³kg. The test liquid 1.0².0ml was injected in the side of the quadriceps area by sterile operation method and the muscle of injection site was cut by longitudinal after 48h. The results showed that the part of administration was not adverse reactions, so the compound florfenicol injection is not irritation. Four rabbits were used to do eye stimulation test, both eyes were observed for half an hour before the experiment properly, and it can be used to test. One side of eyes was dropped drugs and another eye was dropped physiological saline, the eye of control group immediately opened, and another eye opened at 2-3min after drop drugs. We observed conjunctiva without edema, photophobia, and tearing stimulation at 30, 60, 90 and 120min after administration. The results of eye irritation showed that compound florfenicol injection is non-irritating based on evaluation criteria3. The pharmacokinetic studies of test animal rabbits and target animal calves were carried out. The drug concentration's data were analyzed with WinNonlin5.2 pharmacokinetics software to get pharmacokinetic parameters. The pharmacokinetic parameters of florfenicol in rabbits were as follows: T1/2α1.983±0.278h, T1/2?35.54±2.804h, AUC54.52±7.121μg·mL^-1·h, Tmax1.577±0.065h, Cmax5.943±0.211μg·mL^-1. The pharmacokinetic parameters of meloxicam in rabbits were as follows: T1/2α3.529±0.083h, T1/2?138.4±18.32h, AUC25.44±9.059μg·mL^-1·h, Tmax5.155±0.077h, Cmax1.016±0.058μg·mL^-1.The pharmacokinetic parameters of florfenicol in calves were as follows: T1/2α4.767±0.694h, T1/2?34.83±6.771h, AUC 177.1±11.67μg·mL^-1·h, Tmax2.367±0.119h, Cmax5.281±0.239μg·mL^-1. The pharmacokinetic parameters of meloxicam in calves were as follows: T1/2α3.807±0.137h,T1/2?61.38±14.84h,AUC54.52±7.121μg·mL^-1·h,Tmax6.071±0.177h,Cmax1.598±0.084μg·mL^-1. The results showed that pharmacokinetic parameters of florfenicol and meloxicam in rabbits and calves belongs to two compartment open model with first order absorption, pharmacokinetic profile of the same drug in the two animals is consistent.