| Tylvalosin, also known as Acetylisovaleryltylosin tartrate, is a novel macrolide antibiotic for animals which is mainly used in the prevention and treatment of acute or chronic respiratory system and digestive system disease. The antibacterial spectrum of tylvalosin and tylosin is similar, which has high antibacterial activity against mycoplasma, spirochete, most of gram positive microbes and a part of gram-negative bacteriums. Tylvalosin has been widely applied in clinic because of high efficient, low toxicity, low-residue and no cross-resistance with other macrolides.A high performance liquid chromatography-UV method was developed for the determination of the content of tylvalosin granules and tylvalosin in pig plasma. The limit of detection and limit of quantification were 0.05 ?g/m L and 0.1 ?g/m L, respectively. For the detection of the content of tylvalosin granules, the mean recovery was 93.64±3.45%, and the intra-day and inter-day relative standard deviations were were less than 2%. For the determination of tylvalosin in pig plasma, the mean recovery was 86.75±2.25%, and the intra-day and inter-day relative standard deviations were less than 3%. A higher sensitive, precise and accurate method was obtained.The single factor experiment was used to select formulation of tylvalosin granules, and 20% of tylvalosin, 55% of shaping agent, 20% of disintegrating agent and 5% of antifoaming agents were selected. The technological conditions were optimized using the orthogonal experiment design, and the tylvalosin granules were prepared by cold spraying. The stress testing which the preparations were placed under the condition of high temperature, high humidity and strong light for ten days and the accelerated testing which the samples were placed under the conditions of temperature of 40±2°C and relative humidity of 75 ± 5°C for six moths were used to evaluat the stability of preparation. The results indicated that no significant changes in the appearance, content, granularity, dissolubility and degradation product of samples were observed, which the tylvalosin granules with good stability was obtained.Twelve healthy pigs were randomly assigned to two groups, six pigs were given a single intragastric administration of 20% tylvalosin premix(20 mg.kg-1 b.w.), and another six pigs were given 20% tylvalosin granules at the same dose. The tylvalosin in plasma were determined by high performance liquid chromatography-UV. The main pharmacokinetic parameters were determined by means of the Win Nonlin5.2.1 corresponded to the noncompartmental pharmacokinetic model. The main pharmacokinetic parameters of 20% tylvalosin premix were as follows: t1/2? 2.29±0.35 h, tmax 1.42±0.49 h, Cmax 0.96±0.44 ?g/m L, AUC0-last 3.19±1.02 ?g·h/m L, MRT 3.58±0.62 h, CL/F 6.02±1.81 L/h/kg, Vd/F 19.92±6.9 L/kg. The main pharmacokinetic parameters of 20% tylvalosin granules were as follows: t1/2? 2.22±0.2 h, tmax 1.63±0.49 h, Cmax 1.14±0.28 ?g/m L, AUC0-last 4.53±0.86 ?g·h/m L, MRT 3.89±0.19 h, CL/F 4.19±0.75 L/h/kg, Vd/F 13.54±3.47 L/kg. The main pharmacokinetic parameters were analysed by SPSS software, and the results showed that no significant statistical difference of the pharmacokinetic parameters of t1/2?, tmax and MRT were observed(p > 0.05). And a significant statistical difference of the value of AUC0-last, Vd/F, CL/F were observed(0.01 < p < 0.05), which the value of AUC0-last of 20% tylvalosin granules was slightly higher than the 20% tylvalosin premix. The results indicated that the 20% tylvalosin granules was rapidly absorbed and eliminated relatively slowly. The relative bioavailability was(147.8±28.7)%.A good stability and palatability of tylvalosin granules were observed in this study. A new formulation of tylvalosin which can be used for veterinary clinical was obtained. The studies of comparative pharmacokinetics of 20% tylvalosin granules and 20% tylvalosin premix provided a scientific basis for the rational use of veterinary drug in clinic. |
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