The Study Of Amikacin On Clinical Safety And Pharmacokinetics In The Dog

As the second generation of aminoglycoside amikacin mainly acts on bacteria 30S subunit, thereby inhibiting bacterial protein synthesis, and the normal protein synthesis will be affected by abnormal protein synthesis, all of this will impeding the release of it; by inhibition of protein synthesis of the bacterial cell membrane, amikacin can affect bacterial cell membrane barrier function, therefore, amikacin can more easily enter the cytoplasm of bacteria to enhancing the function of drugs. Amikacin is widely used in clinical practice of the digestive system, respiratory system and urinary tract infection due to the susceptible strains as well as the other aminoglycoside antibiotic-resistant bacteria. The test used the. amikacin injection, which does not absorb oral, but when subcutaneous and intramuscular inject, absorb, distribut and eliminate rapidly and widely distributed in the body, and have a significant PAE. In this paper, through amikacin clinical safety trials in the dog and pharmacokinetics studied, to provide more detailed guidance on the clinical use of amikacin.Experiment one The study of amikacin on clinical safety in the dogAccording to the Ministry of Agriculture bulletin (No.1425) "Safety testing guidelines of pet's drugs on the target animal" to valuates the clinical safety of amikacin injection in the dog. This experiment selected 30 healthy adult dogs were randomly divided into five groups, with six dogs in each grup, half male and half female. According to the clinical recommended dose of Amikacin (10 mg-kg-1) as the basis, respectively set the 10 times clinical recommended therapeutic dose group (100 mg�kg-1),5 times clinical recommended therapeutic dose group (50 mg�kg-1),3 times clinical recommended therapeutic dose group (30 mg�kg-1), the clinical recommended therapeutic dose group(10 mg�kg-1) and the control group (0 mg�kg-1). Subcutaneous injection for 21 consecutive days, at the trial periods, by comparing the changes of clinical symptoms of dogs, when they were at the 1st day before the test, the 4th day after administration, the 7th day after administration, the 14th day after administration, the 21st day after administration and the 21st day after ending the test, such as blood CBC indicators, blood biochemical indicators, urine test indicators and histopathology to evaluate the safety of amikacin injection. The results showed that:compared with the control group, there is no significant difference(p> 0.05) between the clinical recommended therapeutic dose group,3 times the clinical recommended therapeutic dose group and 5 times the clinical recommended therapeutic dose group after 14th day administration.Experiment two The pharmacokinetics study of amikacinCombining with reports on HPLC determination of amikacin at home and abroad, choiced the pharmacokinetic method of the veterinary Amikacin injection in the dogs. The test chose eight healthy adult dogs, each dog was subcutaneous injected with a single dose 10 mg�kg-1 of Amikacin injection, collected the blood sample at different time, according to the pre-experimental design approached to plasma samples and tested its plasma concentration, the plasma concentration-time curve were analysed by 3P97 pharmacology software. In the range of 0.5-50 ?g-mL-1, the plasma concentration of Amikacin showed good linearity, and the linear equation was y=100083x+24570, R2=0.997. In this pharmacokinetic method, the plasma concentration- time curve of single dose administration of Amikacin corresponds with Two-compartment model with first order absorption. Its main pharmacokinetic parameters include:time-to-peak (T<peak>) is 0.686�0.06 h, peak-concentration (Cmax) is 6.33�0.54 ?g�L-1, plasma half-life elimination (T1/2bate) is 1.779�0.13 h, the area under the curve (AUC) is 104.9�8.46 ?g*h�L-1.The results show that:after subcutaneous injected Amikacin in adult dogs, it is widely distributed, and Amikacin is the short-term chronic-to-eliminate drug in the body. In this experiment, the analysis method of liquid chromatography is fulfiling the evaluation requirement of clinical effect, it has the advantages of accurate, sensitive and reproducible.