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斑蝥酸钠对依鲁替尼在大鼠体内代谢的影响

Effects of sodium cantharidinate on the metabolism of ibrutinib in rats
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摘要 目的建立同时检测依鲁替尼及其代谢产物(PCI-45227)的高效液相色谱(HPLC)法,研究斑蝥酸钠对依鲁替尼在大鼠体内代谢的影响。方法按照体重将SD大鼠随机分为2组:对照组、实验组,每组9只。对照组腹腔注射0. 9%NaCl 0. 5 mL·kg^(-1),实验组腹腔注射斑蝥酸钠注射液0. 5 mL·kg^(-1),连续10 d。第11天给药后,2组均灌胃给予依鲁替尼10 mg·kg^(-1)。于给药后不同时间点采集血样,以HPLC法测定大鼠血浆中依鲁替尼和PCI-45227的浓度,以DAS 3. 0计算主要药代动力学参数。结果依鲁替尼:对照组和实验组的C_(max)分别为(1019. 43±74. 88),(1196. 58±81. 64) ng·mL^(-1);这2组的AUC_(0-∞)分别为(1. 10±0. 25)×10~4,(1. 34±0. 10)×104ng·h·mL^(-1)。PCI-45227:这2组的C_(max)分别为(230. 59±15. 36),(167. 28±38. 99) ng·m L^(-1);这2组的AUC0-∞分别为(3203. 80±345. 78),(2443. 95±680. 71) ng·h·mL^(-1)。给予斑蝥酸钠后,依鲁替尼的C_(max)和AUC_(0-∞)均明显增加,而代谢物PCI-45227的C_(max)和AUC_(0-∞)均明显降低。结论斑蝥酸钠能可以增加依鲁替尼的血浆暴露量,减少PCI-45227的血药浓度。斑蝥酸钠能抑制依鲁替尼在大鼠体内的代谢。 Objective To study the effect of sodium cantharidinate on the metabolite of ibrutib in rats using high performance liquid chromatography( HPLC) method. Methods Sprague Dawley( SD) rats were randomly divided into two groups: control and experimental groups,each group had 9 rats. On the first 10 days,the control group was intraperitoneally injected with normal saline 0. 5 m L·kg^-1,and the experimental group was intraperitoneally injected with Disodium Cantharidinate Injection 0. 5 m L·kg^-1. After 11 days of administration,the two groups were given gavage to ibrutinib 10 mg·kg^-1. Blood samples were collected at different time points after administration. The concentration of ibrutinib and PCI-45227( ibrutib metabolite) in rat plasma was determined by HPLC,and the main pharmacokinetic parameters were calculated by DAS 3. 0. Results The ibrutinib: Cmaxin control group and experimental group was( 1019. 43 ± 74. 88) and( 1196. 58 ± 81. 64) ng · mL^-1,and AUC0-∞ in the 2 groups was( 1. 10 ± 0. 25) × 10^4 and( 1. 34 ± 0. 10) × 10^4 ng·h·mL^-1,respectively. The PCI-45227: Cmaxin the 2 groups were( 230. 59 ± 15. 36) and( 167. 28 ± 38. 99) ng · mL^-1,respectively.AUC0-∞ in the 2 groups were( 3203. 80 ± 345. 78) and( 2443. 95 ± 680. 71)ng·h·mL^-1,respectively. The Cmax and AUC0-∞ of ibrutinib wereincreased significantly after giving sodium cantharidinate,while the Cmaxand AUC0-∞ of PCI-45227 were decreased obviously. Conclusion It is indicated that sodium cantharidate can increase the plasma exposure of ibrutinib and reduce the blood concentration of PCI-45227. That is,sodium cantharidate inhibits the metabolism of ibrutinib in rats.
作者 陈克莉 袁红昌 李双龙 朱永良 邱相君 CHEN Ke-li;YUAN Hong-chang;LI Shuang-long;ZHU Yong-liang;QIU Xiang-jun(Medical College of Henan University of Science and Technology,Luoyang 471023,Henan Province,China;The First Affiliated Hospital of Xinxiang Medical University,Xinxiang 453100, Henan Province,China)
出处 《中国临床药理学杂志》 CAS CSCD 北大核心 2019年第2期161-164,共4页 The Chinese Journal of Clinical Pharmacology
关键词 高效液相色谱法 斑蝥酸钠 依鲁替尼 药物相互作用 HPLC sodium cantharidate ibrutinib drug interaction
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