Pharmacokinetics Of Tilmicosin Phosphate In Swine

Tilmicosin is macrolide livestock antibiotics. Because of its special antimicrobial activities and pharmacokinetic characteristics, tilmicosin can inhibit all the gram positive bacteria, parts of gram negative bacteria, mycoplasma, spirochetes, especially for actinobacillus pleuropneumoniae, pasteurella hemolytica, pasteurella multocida and livestock mycoplasma. Tilmicosin is used to treat the infectious diseases of swines, chickens, goats, cows and so on. However, because it can not be readily soluble in water, the efficiency of tilmicosin by oral administration and injection can be affected. In order to change the application status of tilmicosin and to broaden the scope of its application, tilmicosin phosphate is prepared. The detection of tilmicosin in swine plasma by an improved HPLC method, and the pharmacokinetic process and characteristics of tilmicosin phosphate soluble powder in swines were studied to provide a scientific basis for the rational use of drugs in livestock and poultry.The detection method of tilmicosin in swine plasma was improved in this study by high performance liquid chromatograph (HPLC). Under the testing conditions of C18 column (4.6×50mm,5μm), the detection wavelength at 280 nm, the flow rate 1.0 mL/min, mobile phase of acetonitrile:tetrahydrofuran:dibutyl amine phosphate buffer:water= 10:5:5:80. Treatment conditions of plasma:SPE column were washed with 10 mL pure water and 12 mL acetonitrile-water (35:65, v:v), collected 2.5 mL eluent (0.1 mol/L ammonium acetate-methanol-acetonitrile) in a graduated tube, blowed it to near dryness by nitrogen in 30℃ water bath, dissolved it in mobile phase, measured 10 μL for HPLC analysis. The results of chromatogram displayed peak time and peak shapes were perfect, response was well, tilmicosin was separated from the other components. The results showed the good linear relationship between the peak area and the corresponding concentration, the linear range was from 0.05 to 25μg/mL (R2-09998), the average recovery is above 82.6%.To investigate pharmacokinetic characteristics of tilmicosin phosphate in swine, HPLC method was used to detect tilmicosin concentrations in the tested swine plasma after given different doses of tilmicosin phosphate by oral administration and a certain dose of tilmicosin phosphate by intravenous injection. The results showed that after the the swines took tilmicosin phosphate soluble powder orally or by intravenous injection, drug was absorbed and distributed quickly, but it was eliminated slowly. The elimination half-life was far greater than the absorption half-life. The drug was conform to the two-compartment model. After the injection of tilmicosin phosphate soluble powder at the dose of 5 mg/kg, area under concentration-time curve (AUC0-∞) was 3.0656 ± 1.3426 μg/mL-h, and AUC0-∞ of tilmicosin phosphate soluble powder medium dose group was 2.7377 ± 0.5642 μg/mL·h. The absolute bioavailability of tilmicosin phosphate is 93.02%. After given different doses of tilmicosin phosphate soluble powder by oral administration, the results showed that maximum concentration (Cmax) and AUC0-∞ were almost proportional to the amount of given medicines and indicated that the pharmacokinetics of tilmicosin phosphate soluble powder in swines is the first-order kinetic process. After given 10%tilmicosin soluble powder (53.7 mg/kg) orally, Cmax was 0.1062 ± 0.0361 μg/mL and Tmax was 1.9671 ± 0.5086 h. After given medium dose of 10% tilmicosin phosphate soluble powder orally, Cmax was 0.1161 ± 0.0257 ug/mL and Tmax was 2.1286 ± 0.5892 h. There was no significant difference between them. The results indicate that 10% tilmicosin phosphate soluble powder can be rapidly absorbed and eliminated slowly. According to the important evaluation index of bioequivalence, the pharmacokinetic process and characteristics, tilmicosin phosphate soluble powder and control tilmicosin soluble powder have the same bioequivalence.