目的 研究载天冬酰胺酶(asparaginase,AN)自组装透明质酸-聚乙二醇/α-环糊精纳米囊在SD大鼠体内的药动学和生物等效性。方法 将大鼠随机分为两组,分别静脉给予AHAPs和游离AN后,测定不同时间点两组大鼠血浆样品中AN的活性。采用DAS2.1.1软件计算药动学参数。对AHAPs和游离AN的生物等效性进行评价。结果 AHAPs和游离AN的主要药动学参数AUC0-48 h分别为(132.26±1.59)和(46.38±1.98)U·h·mL-1,MRT0-48 h分别为(3.64±0.04)和(1.76±5.99)h,tmax分别为(0.75±0)和(0.08±0)h。通过比较,AHAPs的AUC0-48 h、MRT0-48 h和tmax分别为游离AN的2.85、2.07和9.37倍。AUC0-48 h、AUC0-∞和ρmax的90%可置信区间分别为77.0%~78.5%,77.0%~78.5%,94.4%~96.0%。tmax经非参数法检验具有显著性差异(P<0.05)。结论 AHAPs能提高AN在大鼠体内的生物利用度,并有效延长其在大鼠体内的作用时间。AHAPs与游离AN不具有生物等效性,且AHAPs在大鼠体内的药动学特性更优。
Abstract
OBJECTIVE To investigate the pharmacokinetics and bioequivalence of hyaluronic acid-graft-poly(ethylene glycol)/α-cyclodextrin nanocapsules loaded with asparaginase(AHAPs) in SD rats. METHODS Rats were randomly divided into two groups. After intravenous injecting AHAPs and free AN, the activity of AN in two groups was assayed at different time points. The pharmacokinetic parameters were calculated by software DAS2.1.1 and the bioequivalence of free AN and AHAPs was judged. RESULTS AUC0-48 h of AHAPs and free AN were (132.26±1.59) and (46.38±1.98) U·h·mL-1. MRT0-48 h of AHAPs and free AN were (3.64±0.04) and (1.76±5.99) h. The tmax of AHAPs and free AN were (0.75±0) and (0.08±0) h, respectively. The results showed that AUC0-48 h, MRT0-48 h and tmax of AHAPs increased to 2.85, 2.07 and 9.37 times, respectively, as compared with free AN. The 90% confidential intervals of AUC0-48h, AUC0-∞ and ρmax of tested formulation were 77.0%-78.5%, 77.0%-78.5%, 94.4%-96.0%, respectively. The tmax checked by nonparametric method has significant difference (P<0.05) between AHAPs and free AN. CONCLUSION AHAPs can improve the bioavailability and extend the action time of AN in rats. AHAPs and free AN were not bioequivalent. And AHAPs had better pharmacokinetics properties in rats.
关键词
天冬酰胺酶 /
纳米囊 /
体内 /
药动学 /
生物等效性
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Key words
asparaginase /
nanocapsule /
in vivo /
pharmacokinetics /
bioequiavailability
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中图分类号：
R969.1
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脚注
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基金
重庆市科委资助项目(cstc2015jcyjBX0027)
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