Bioavailability And Tissue Distribution Of Tilmicosin In Ducks

AIM: To establish the method of detection tilmicosin (TMS) after extraction and purification from the plasma and tissues of ducks, using reversed-phase high performance liquid chromatography (RP-HPLC). And to study on pharmacokinetics, absorption and distribution of the TMS following intravenous and oral administration in ducks. In order to provide evidence for veterinary clinical medication.METHODS: The plasma and tissues samples were collected in different intervals after intravenous and oral administration of TMS. The samples were determined by using RP-HPLC after solid-phase extraction and nitrogen dryer adding suitable mobile phase. The concentration-time data of TMS in plasma and tissues were analyzed with 3P97 pharmacokinetics program and the bioavailability was calculated by dose calibration method.RESULTS: The correlation of calibration curve were all good, which correlation coefficient were more than 0.9990. The limit of detection (LOD) was 0.0125μg/mL, 0.005μg/g, 0.005μg/g, 0.01μg/g, 0.02μg/g and 0.0125μg/g in plasma, muscle, skin, lung, liver and kidney, respectively. The average extraction recovery was more than 75% from the tissues and plasma. The intra-day coefficient of variations and inter-day coefficient of variations were less than 5% and 10% respectively. The ducks received intravenous and oral administration of TMS, The results indicated the plasma drug concentration-time data were fitted two-compartment open models. After intravenous administration (5mg/kg·B·W), the disposition half-life (t_1/2α) of the drug was 0.076±0.0098h, whereas the elimination half-life (t_1/2β) of the drug was 7.31±0.63h. The area under the serum concentration-time curve (AUC) was 4.50±0.30 (μg/ mL)·h. The total body clearance (CL_b) was 1.12±0.069 L/(kg·h). The apparent distribution volume (V_d) was 10.73±0.78 L/kg. After oral administration (20mg/kg·b·w), the disposition half-life (t_1/2α) of the drug was 1.76±0.49h, whereas the elimination half-life (t_1/2β) of the drug was 25.70±4.74h, the absorption half-life (t_1/2Ka) was 0.090±0.0092h. The area under the serum concentration-time curve (AUC) was 14.03±2.54 (μg/mL)·h. The total clearance of TMS (CL_b) was estimated to be 1.46±0.22 L/(kg·h). The time-point of maximum plasma concentration of the drug (T_max) and the maximum plasma concentration (C_max) were calculated as 0.47±0.035h and 0.75±0.056μg/mL. The bioavailability was 78.47±0.15%. The study of distribution revealed that tilmicosin in penetrating the organizations ability to absorb quickly and eliminate slow, with the exception of lung medicine at the curve in the two-compartment model, the remaining were in a single-compartment model of absorption. The curve of concentration- time in lung, liver, kidney, muscle and skin were C₁=24.05e^-0.28t+5.08e^-0.013t-29.13e^-0.35t, C₂=6.03 (e^-0.029t-e^-0.44t), C₃=5.31 (e^-0.034t-e^-0.52t) ,C₄=2.66 (e^-0.020t-e^-0.22t) and C₅=2.71 (e^-0.032t-e^-0.19t) .