Comparative Pharmacokinetic Of Tilmicosin Solution And Tilmicosin Phosphate Powder In Broilers

Tilmicosin is a special antibiotic for livestock and poultry which is a semisynthetic hydrolysate of tylosin.It feature broad antimicrobiol spectrum,effective antimicrobiol action,widely distributed in tissue,fast absorption when taken internally and were given hypod-ermic injection,excellent penetrability,the effects last longer,no carcinogenesis,tetratogenesis and mutagenesis.Tilmicosin belongs to macrolide antibiotics and it mainly inhibit bacteria protein synthesis to exert antimicrobiol effects by uniting with 50S subunits of bacteria ribos-omes to prevent the action of transpeptidases and disturb the displacement of mRNA.Tilmicosin Phosphate is a kind of phosphate of Tilmicosin.It dissolves easily in water and its soluble powder can treat chichens respiratory infection which is caused by Mycoplasma gallisepticum(Anti-MG) by taking Tilmicosin in their drinking water directly. By comparing the comparative pharmacokinetics of Tilmicosin Phosphate with Tilmicosin solution in chickens to obtain the related pharmacokinetic parameters,learn the regulation that 10% tilmicosin solution and 10% tilmicosin phosphate powder concentration changed over time. And compared the pharmacokinetic parameters for showing the different characteristics of 10% tilmicosin solution and 10% tilmicosin phosphate powder.This research result can not only provide the basis for guiding design of new developed medicine 10% tilmicosin phosphate powder and rational clinical use of drugs,but also providing references for estimating the eliminable dynamic change,absorption perperty and elimination rule on residues in chickens further.This study has compared pharmacokinetic of the market medicine 10% tilmicosin solution and new developed medicine 10% tilmicosin phosphate powder which studied on healthy broilers. Choose the initial weight about 1.7 kg of 24 broiler chickens, randomly divided into 2 groups, each group of 12 (male female half), the first group 1-12 irrigation take 10% tilmicosin phosphate powder, the other group of 13-24, irrigation take 10% tilmicosin solution, blood after infusion medicine according to the stipulated time, and extract medicines in plasma with methyl alcohol and trichloromethane, than using high performance liquid chromatography (HPLC) method to determine plasma drug concentration in the different time points.Measured blood drug concentration-time data respectively using Winnonlin5.2 pharmacokinetic analysis software calculating pharmacokinetic parameters.We established the method of detect the concentration of tilmicosin in plasma by HPLC. Extracted tilmicosin in plasma using methanol and chloroform, detect concentration of tilmicosin with ultraviolet detector of HPLC.The flowing phase include acetonitrile, tetrahydrofuran, butyl amine phosphate buffer, ultrapure water (110:55:25:810, V/V), detection wavelength of 286 nm, the flow rate of 1 mL/min. The results show that the test tilmicosin standard working fluid in 0.05～10 mg/L respectively had good linear relationship within (R2≥0.9998). Added tilmicosin in the plasma concentration of 5.0,0.5,0.05 mg/L, the recovery is 97.0%～99.8%;Intra-day and inter-day coefficient of variation was less than 7.2% and 7.7% respectively.After administration single dose of market medicine that is 10% tilmicosin solution,the main pharmacokinetics parameters were T1/2β 17.316 h, Tmax 1.083 h, Cmax 0.399 μg/mL, AUC 1.891 (μg/mL/hr), MRT 8.286 h, Vd 10.176 hr*mg/mL, CL(B) 74.869 mL/min/kg. After administration single dose of new developed medicine that is 10% tilmicosin phosphate powder, the main pharmacokinetics parameters were T1/2β 13.207 h, Tmax 1.333 h, Cmax 0.372 μg/mL, AUC 1.813 (μg/mL/hr), MRT 7.612 h, Vd 12.011 hr*mg/mL, CL(B) 103.744 mL/min/kg.The T1/2β was fast after oral administration in elimination comparing to the reference substance 10% tilmicosin solution. The Tmax was slightly delay than the reference substance. The peak concentration (Cmax) was slightly lower than the reference substance, but still higher than reported what the MICs of tolmicosin to mycoplasma gallisepticum ranged from 0.0125 to 0.1 μg/mL. The mean area under the curve (AUC) and the mean residence time (MRT) were lower than the reference substance respectively. The Vd and CL(B) were higher than the corresponding reference substance respectively. But the statistical analysis shows that the pharmacokinetic parameters were no significant difference compared with the reference substance (p> 0.05).The result showed tha the absorption was fast, the elimination was slow, the distribution in body was wide after oral 10% tilmicosin solution and 10% tilmicosin phosphate powder oral dosing in broilers, and then the effective blood drug concentration could maintain a long time. 10% tilmicosin phosphate powder and 10% tilmicosin solution shared similar features on the pharmacokinetics. Formulate dosage regimen of new developed medicine that 10% tilmicosin phosphate powder can refer to the dosage regimen of market medicine that is 10% tilmicosin solution in clinical practice.10% tilmicosin phosphate powder not only can dissolved in water but also mixed with feed by oral administration.In addition,10% tilmicosin solution will volatilize to increasing the concentration,but 10% tilmicosin phosphate powder not.