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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[hyaluronic acid-graft-poly(ethylene glycol)/α-cyclodextrin nanocapsules loaded with asparaginase,AHAPs]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。
OBJECTIVE: To study the effect of asparaginase (AN) self-assembled hyaluronic acid-polyethylene glycol / α-cyclodextrin nanocapsules loaded with asparaginase AHAPs] pharmacokinetics and bioequivalence in SD rats. Methods The rats were randomly divided into two groups. After the AHAPs and the free AN were administered intravenously, the AN activity in the plasma samples from different time points was determined. Pharmacokinetic parameters were calculated using DAS2.1.1 software. The bioequivalence of AHAPs and free AN was evaluated. Results The main pharmacokinetic parameters (AUC0-48 h) of AHAPs and free AN were (132.26 ± 1.59) and (46.38 ± 1.98) U · h · mL -1, respectively, and MRTs of 0-48 h were (3.64 ± 0.04) And (1.76 ± 5.99) h, tmax were (0.75 ± 0) and (0.08 ± 0) h, respectively. By comparison, the AUC0-48 h, MRT0-48 h and tmax of AHAPs were 2.85, 2.07 and 9.37 fold, respectively, for free AN. The 90% confidence intervals of AUC0-48 h, AUC0-∞ and ρmax were 77.0% -78.5%, 77.0% -78.5%, 94.4% -96.0%, respectively. tmax by nonparametric test was significantly different (P <0.05). Conclusion AHAPs can improve the bioavailability of AN in rats and prolong its action time in rats. AHAPs and free AN are not bioequivalent, and AHAPs have better pharmacokinetic properties in rats.