| THmicosin is a novel macrolide antibiotic with a wide therapeutic uses against bacteria and mycoplasmae. It has high antibacterial effects and low toxicity or adverse effect, and it shows promising prospect of application in clinical veterinary practice. In this study, tilmicosin solution was successfully developed. Stability and pharmacokinetics of this solution were studied.Temperature accelerated test (6monthes) under 40℃ and long-term stability test (10monthes) also had undergone. The experimental results showed that tilmicosin content had a descent among rang of 3.6%~5.0% at temperature accelerated test under 40℃ and a rang of 3.0%~3.5% at long term stability test at room temperature(about 16-25℃). Both of two experimental results showed that tilmicosin solution were stable either to heat or to room temperature. The tilmicosin solutions were complied with the requirement of drug preparation.The high performance liquid chromatography (HPLC) methods were developed for determination of tilmicosin concentration in chicken plasma and tilmicosin residues in chicken lungs, respectively. The lung tissues were extracted with acetonitrile and 0.1M potassium dihydrogen phosphate buffers. The extracts purified by C18 solid-phase extraction cartridges. The eluates were determined by HPLC at 288nm. Limits of detection (LOD) were 0.025 ug/mL for tilmicosin in plasma and 0.025ug/g for tilmicosin in lung, respectively. Limits of quantification (LOQ) were 0.05 ug/mL for tilmicosin in plasma and 0.05ug/g in lung, respectively. Recoveries were 85.1%~98.1% for chicken plasma fortified at 0.05, 0.5, 5ug/mL and 90.2% ~ 98.8% chicken lung fortified at 0.05, 0.5, 5ug/g, respectively. Coefficients of variation were in the range of 3.5%~8.7% for chicken plasma and 2.36%~11.8%for chicken lungs, respectively. The method complied with the requirement of residue analysis and correlative study.Broiler chickens were given a single oral dose of tilmicosin of 50mg/kg body weight. Pharmacokinetic analysis of plasma concentration-time data for tilmicosin was carried out using a computer program (3p97,China Pharmacology Association). Plasma concentration-time data after oral administration were best described by a two-compartment open model. The parameter of male chicken as following: t1/2a0.948±0.043h, t1/2Ka0.091±0.008h, t1/2B24.18±3.946h: AUC 15.563±0.342 (ug/mL)*h, CL(s) 3.214±0.070mg/kg/h/(ug/mL), Tmax 0.413±0.035h, Cmax 0.868±0.027ug/mL. The parameter of female chicken were as following: t1/2a0.757±0.454h, t1/2Ka 0.104±0.045h, t1/2B29.041±10.288h; AUC23.788±8.181 (ug/mL)*h, CL(s)2.251 ±0.652 mg/kg/h/(ug/mL) , Tmax0.390±0.145h , Cmax 1.297±0.272ug/mL. Pharmacokinetic analysis of lung concentration-time data for tilmicosin was also carried out using a computer program (3p97,China Pharmacology Association). Lung concentration-time data after oral administration of 50mg/kg body weight were also best described by a two-compartment open model. The parameter of male chicken were as following: t1/2 a 为 2.28S±0.657h , t1/2Ka1.090±0.193h, t1/2B 为 37.606±4.474h, AUC530.797±48.050 (ug/g)*h, CL(s) 0.095±0.008mg/kg/h/(ug/g), Tmax 5.256±0.442h, Cmax 9.044±0.016ug/g. The parameters of femalechicken were as following: t1/2a1.556±0.825h, t1/2Ka0.732±0.101h, t1/2p23.304±2.320h, AUC395.073±12.095 (ug/g)*h, CL(s)0.127±0.004 mg/kg/h/(ug/g), Tmax3.584±0.440h, Cmax 10.691±0.542ug/mL. The experiment results showed that Tilmicosin were absorbed fast, distributed widely in the organism of broilers and eliminated slowly. It has good tissue penetration and reaches high concentration in the lungs. The concentrations of tilmicosin in lungs were 10.42 and 8.24 folds as higher as that in plasma in male and female chicken, respectively. The student t-test showed that AUC and other main parameters were statistically significant difference between male and female chicken.
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