尼奥宁在Beagle犬体内的药动学及其生物利用度研究  

Pharmacokinetics and bioavailability study of neoline in Beagle dogs

作　　者：龚小红[1] 赵梦杰[1] 袁岸 李燕[1] 熊亮[1] 彭成[1] 李芸霞[1] 

机构地区：[1]成都中医药大学药学院,中药材标准化教育部重点实验室,中药资源系统研究与开发利用省部共建国家重点实验室培育基地,四川成都611137

出　　处：《中国中药杂志》2015年第13期2656-2660,共5页China Journal of Chinese Materia Medica

基　　金：国家重点基础研究发展计划(973)项目(2012CB723502);四川省杰出青年基金项目(2013JQ0018);四川省科技厅省青年科技创新研究团队专项计划项目(2014TD0007,2015TD0028)

摘　　要：研究尼奥宁在Beagle犬体内药动学及其绝对生物利用度,为其进一步研究提供理论基础。实验血浆样品用10%氨水碱化后用乙酸乙酯液液萃取,采用UPLC-Q-TOF-MS测定血浆中尼奥宁浓度。Beagle犬分别灌胃6 mg·kg-1或静脉给药1mg·kg-1进行尼奥宁体内药代动力学和绝对生物利用度研究。血浆样品处理方法中,尼奥宁在0.1～4 mg·L-1和2～100μg·L-1均呈良好线性关系（R2=0.998 2,0.994 5）,日内及日间精密度RSD均小于5.0%,准确度RE在90.0%～115%,回收率均大于80%。灌胃或静脉给药后,尼奥宁t1/2分别为（313.88±63.18）,（236.33±229.84）min,AUC0-∞分别为（58 027.40±14 132.69）,（473 578.02±82 333.08）min·μg·L-1,其绝对生物利用度为（73.15±10.29）%。结果表明UPLC-Q-TOF-MS分析血浆尼奥宁灵敏、可靠、专属性强,可用于尼奥宁的体内药动学分析;尼奥宁在Beagle犬体内生物利用度较高显示其良好的吸收特性,也为进一步研究奠定基础。This paper is aim to investigate the pharmacokinetics and absolute bioavailability of neoline in Beagle dogs, and provide a theoretical basis for further study. Ethyl acetate was used for liquid-liquid extracting after 10% ammonia alkalizing. The method of UPLC-Q-TOF-MS was established for the determination of neoline plasma concentrations. Beagle dogs were orally or intravenously ad- ministered with neoline for pharmacokinetic and absolute bioavailability study. Good linear relationship of neoline was found over the range of 0. 1-4 mg · L-1 （R2 =0. 998 2）and 2-100 μg · L-1 （R2 =0. 994 5）. Intra-and inter-day precision, expressed as the relative standard （RSD） were less than 5.0%. Accuracy, expressed as the relative error （RE） was within 90.0% -115%. The recovery of ne- oline in dog plasma was more than 80%. After 6 mg · kg-1 for ig and 1 mg· kg-l for iv administration of neoline, the main pharmaco- kinetic parameters were analyzed with Winnonlin software, t1/2 were（313. 88 ± 63. 18 ）, （236. 33 ± 229. 84） min, and AUC0-∞ were （58 027.40 ± 14 132. 69 ）, （473 578.02 ± 82 333.08 ） min ·μg· L- 1 for ig and iv administration respectively. The absolute bioavail- ability was （73. 15 ± 10. 29 ）%. The method of UPLC-Q-TOF-MS described in the report was sensitive, reliable and specific, and suit- able for pharmacokinetic study of neoline in Beagle dog. The high absolute bioavailability of neoline in dog suggested good absorption of neline which was worth of further investigation.

关 键 词：尼奥宁 UPLC-Q-TOF-MS 药动学 绝对生物利用度 

分 类 号：R285.5[医药卫生—中药学]