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引用本文:何子聪,徐泉玉,袁艳娟,邵卿.两性霉素B复合磷脂纳米脂质体Beagle犬体内药动学研究[J].中国现代应用药学,2022,39(1):97-100.
HE Zicong,XU Quanyu,YUAN Yanjuan,SHAO Qing.Study on Parmacokinetic of Amphotericin B Liposome in Beagle Dogs[J].Chin J Mod Appl Pharm(中国现代应用药学),2022,39(1):97-100.
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两性霉素B复合磷脂纳米脂质体Beagle犬体内药动学研究
何子聪1, 徐泉玉2, 袁艳娟3, 邵卿3
1.南京田家炳中学,南京 210009;2.南京工业大学药学院,南京 211800;3.江苏省药物研究所有限公司,南京 211800
摘要:
目的 采用LC-MS/MS测定Beagle犬血浆中两性霉素B的含量,研究受试物两性霉素B复合磷脂纳米脂质体(liposomal amphotericin B,L-AmB)和参比药物AmBisome在Beagle犬体内的药动学行为。方法 选取成年健康Beagle犬12只,♀♂各半。采用双交叉试验设计,周期间洗脱期为2周。经前肢静脉注射给药(6 mg·kg-1,1.0 mg·mL-1),采集给药前以及给药后各时间点血浆样品,应用经验证的LC-MS/MS方法测定血浆中两性霉素B浓度,DAS 2.1.1中求算药动学参数。结果 Beagle犬静脉注射给予6 mg·kg-1的受试物和参比药物后,动物体内两性霉素B的AUC(0-t)分别为(705 520±178 252),(677 310±166 326)μg·h·L-1Cmax分别为(142 683±29 823),(121 992±37 983)ng·mL-1t1/2分别为(8.9±1.5),(9.7±0.6)h。结论 L-AmB及参比制剂AmBisome在Beagle犬体内的药动学参数差异无统计学意义。
关键词:  两性霉素B复合磷脂纳米脂质体  液相色谱-质谱联用  Beagle犬  药动学  静脉注射  血药浓度
DOI:10.13748/j.cnki.issn1007-7693.2022.01.017
分类号:R917.101
基金项目:
Study on Parmacokinetic of Amphotericin B Liposome in Beagle Dogs
HE Zicong1, XU Quanyu2, YUAN Yanjuan3, SHAO Qing3
1.Middle School of Nanjing Tianjiabing, Nanjing 210009, China;2.School of Pharmacy, Nanjing Tech University, Nanjing 211800, China;3.Jiangsu Provincial Institute of Materia Medica, Nanjing 211800, China
Abstract:
OBJECTIVE To establish an LC-MS/MS method for the determination of amphotericin B in plasma of Beagle dogs, and to study the pharmacokinetic parameters of liposomal amphotericin B(L-AmB) and reference drug(AmBisome) in Beagle dogs.METHODS Twelve adult healthy Beagle dogs, half male and half female, were selected. The design of double cross experiment was adopted, and the period of washout was 2 weeks, 6 mg·kg-1(1.0 mg·mL-1) was injected intravenously. The whole blood was collected before and different timepoints after administration. The concentration of amphotericin B in the plasma was determined by the validated LC-MS/MS method, and the pharmacokinetic parameters were calculated by DAS 2.1.1.RESULTS The main pharmacokinetic parameters of L-AmB and AmBisome were as follows: AUC(0-t) was(705 520±178 252), (677 310±166 326) μg·h·L-1; Cmax was(142 683±29 823), (121 992±37 983)ng·mL-1; t1/2 was(8.9±1.5), (9.7±0.6)h.CONCLUSION There is no significant difference between the Beagle dogs after intravenous injection of L-AmB and the reference drug (AmBisome).
Key words:  liposomal amphotericin B  LC-MS/MS  Beagle dog  pharmacokinetic  intravenous injection  blood concentration
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