五种金霉素预混剂的体外溶出度及其在猪体内的释药特征

In vitro release and in vivosteady-state accumulation features of chlortetracycline premix

为考察五种金霉素预混剂的体外溶出度及在健康猪体内的释药特性,采用高效液相色谱法测定五种金霉素预混剂的体外溶出度;选用体重约16kg的大×长二元健康断奶仔猪48头,随机分成6组,通过在饲料中添加金霉素给药(500mg/kg),进行其在健康猪体内的释药特性研究,采用高效液相色谱法测定血浆及肺组织中金霉素的浓度。体外溶出度结果表明,五种金霉素预混剂在120min内累积溶出度依次为制剂C>制剂A>制剂E>制剂B>制剂D,在12min内溶出度较快,12min以后溶出度接近第120分钟的水平;体内释药试验结果表明,五种金霉素预混剂按500mg/kg(以金霉素计)连续饲喂7d,血药浓度均上升较慢,达峰时间较长,第1次给药后第6～8小时达到峰浓度,制剂A、B、C、E组在第1次给药后第3小时至试验结束,血药浓度均超过0.5μg/mL,而制剂D在第3、4、5天的血药浓度均小于0.5μg/mL。结合临床上金霉素对病原菌的抑菌活性,五种金霉素制剂预防疾病的效果依次为制剂C>制剂A>制剂E>制剂B>制剂D,与体外溶出度的结果相一致。

This experiment was conducted to study the dissolution in vitro and in vivo steady-state accumulation of chlortetracycline（CTC） premixes.Simulated gastric fluids were used to compare the dissolution of CTC premixes.48 health crossed-bred（Yorkshire Landrace） pigs,with an average of 16 kg weight were randomly assigned to six dietary treatments following oral administration of CTC at the dose of 500 mg/kg according to body weight for 7 days.Blood and lung samples were collected at different intervals after administration and CTC concentrations were determined by HPLC.It was found that in vitro dissolution study,the kinetics of CTC release in simulated gastric fluid was complex,starting a curve-sharped increase in the first 12 min,followed by a linear increase and ending in a plateau in 12 to 120 min.The dissolution of CTC were CAEBD.And in vivo steady-state,we fortified 5 aliquots of a drug-free feed with the above premixes at 500 mg/kg CTC.The results showed that 5 brands premixes were similar,Cmax were 6 to 8 h after 1st medicated meals.The CTC plasma concentrations of the A,B,C,E premixes were 0.5μg/mL 3h after 1st medicated meals,however,D premixes were 0.5μg/mL on day 3,4 and 5 after 1st medicated meals. In conclusion,therapeutic concentrations were maintained more consistently in pigs given C,A,E,B premixes than D premixes.