摘要
【目的】以褪黑素溶液为对照,比较褪黑素温敏型原位凝胶在肉鸡皮下给药的药动学特征,为褪黑素温敏型原位凝胶的临床使用提供依据和指导。【方法】采用单次皮下注射温敏型原位凝胶和溶液,将3 mg·kg-1褪黑素对肉鸡给药,分别于给药后0.08、0.16、0.25、0.50、0.75、1、1.50、2、4、6、8、9、24、48、60、72、84、96、108、120 h采集血液,利用高效液相色谱法测定并比较肉鸡血浆中2种给药剂型的褪黑素质量浓度,通过非房室模型分析肉鸡血液中2种给药剂型褪黑素药动学参数,对褪黑素温敏型原位凝胶药动学进行研究。【结果】温敏型原位凝胶组与褪黑素溶液组单剂量皮下注射后在肉鸡血浆中褪黑素药峰质量浓度C max分别为(561.66±0.82)和(890.22±0.20)mg·L^(-1),组间差异显著(P<0.05);达峰时间t max分别为72.00和0.50 h,半衰期T 1/2分别为22.49和0.58 h,平均滞留时间MRT(0-∞)分别为(77.320±2.590)和(1.108±0.002)h·mg·L^(-1),药时曲线下面积AUC(0-∞)分别为(39068.75±1514.00)和(890.70±1.02)h·mg·L^(-1),组间差异均极显著(P<0.01);褪黑素温敏型原位凝胶绝对生物利用度(F)为(43.89±13.84)%。【结论】在相同给药剂量下,温敏型原位凝胶的吸收和消除速率均慢于溶液,表明温敏型原位凝胶可提高褪黑素的吸收与分布。
【Objective】To compare the pharmacokinetic characteristics of melatonin thermosensitive in situ gel administered subcutaneously in broilers with melatonin solution as the control,so as to provide evidence and guidance for the clinical use of melatonin thermosensitive in situ gel.【Method】Broilers were given 3 mg·kg-1 melatonin by a single subcutaneous injection of thermosensitive in situ gel and solution.Blood samples were collected at 0.08,0.16,0.25,0.50,0.75,1,1.50,2,4,6,8,9,24,48,60,72,84,96,108,and 120 h after drug administration,respectively.The melatonin quality concentrations of the two dosage forms in broiler plasma were measured and compared by high performance liquid chromatography.And the pharmacokinetic model of thermosensitive in situ gel was established by analyzing the pharmacokinetic parameters of two dosage forms of melatonin in broiler blood.【Result】The average peak mass concentration(C max)of melatonin in plasma of broilers after a single dose of subcutaneous injection in the thermosensitive in situ gel group and the melatonin solution group was(561.66±0.82)and(890.22±0.20)mg·L^(-1),respectively,and the difference was significant between the two groups(P<0.05).The peak time t max was 72.00 and 0.50 h,the half-life T 1/2 was 22.49 and 0.58 h,the average retention time MRT(0-∞)was(77.320±2.590)and(1.108±0.002)h·mg·L^(-1),respectively.The AUC(0-∞)of the drug time curve was(39068.75±1514.00)and(890.70±1.02)h·mg·L^(-1),respectively,and the difference between the groups was significant(P<0.01).The relative bioavailability(F)of melatonin temperature-sensitive in situ gel was(43.89±14.84)%.【Conclusion】At the same dose,the absorption and elimination rates of temperature-sensitive in situ gel were slower than those of the solution,indicating that temperature-sensitive in situ gel could improve the absorption and distribution of melatonin.
作者
周亚星
王月影
聂芙蓉
刘太宇
ZHOU Yaxing;WANG Yueying;NIE Furong;LIU Taiyu(College of Veterinary Medicine,Henan Agricultural University,Zhengzhou 450046,China;College of Animal Science and Technology,Henan University of Animal Husbandry and Economy,Zhengzhou 450046,China)
出处
《河南农业大学学报》
CAS
CSCD
2023年第3期436-443,共8页
Journal of Henan Agricultural University
基金
河南省科技攻关项目(212102110167)。
关键词
褪黑素
温敏型原位凝胶
肉鸡
高效液相色谱法
药动学
melatonin
temperature sensitive gel
chicken
high performance liquid chromatography
pharmacokinetics
