过氧化氢酶脂质体的药代动力学和生物等效性初步研究

Studies on pharmacokinetics and bioequivalance of catalase Studies on pharmacokinetics and bioequivalance of catalase

摘要:

目的：研究过氧化氢酶脂质体（catalase liposomes，CALP）在SD大鼠体内的药代动力学和生物等效性。方法：采用逆向蒸发法制备了CALP，并测定其粒径、Zeta电位及包封率。将12只雄性SD大鼠随机分为２组，分别静脉注射CALP和游离过氧化氢酶（catalase，CAT），测定给药后不同时间点大鼠血浆中过氧化氢酶的活性。采用DAS 2.1.1软件计算药物代谢动力学参数，并对CALP和CAT进行生物等效性评价。结果：CALP的包封率为（53.72±1.67）%，粒径和Zeta电位分别为（405.40±21.89） nm和（-15.70±3.22） mV。CALP和CAT的主要药物代谢动力学参数AUC0-t分别为（203.22 ± 11.75） U（ml·h）和（50.92±3.51） U（ml·h），Cmax分别为（70.79±1.33） U/ml和（51.48±2.78） U/ml，Tmax分别为（0.58 ± 0.14） h和（0.17 ± 0.00） h。lnAUC、lnCmax 经方差分析和双单侧检验证明差异具有统计学意义（P <0.05）。AUC0-t、AUC0-∞和Cmax的90%可置信区间分别为133.8%~140.1%，132.3%~146.7%，104.7%~107.5%。CALP和CAT的Tmax经非参数法检验差异无统计学意义（P >0.05）。CALP的相对生物利用度为（399.1±23.1）%。结论：CALP提高了过氧化氢酶的生物利用度，CALP与CAT不具有生物等效性。

Abstract:

Objective：To study the pharmacokinetic and bioequivalence of catalase liposome（CALP） in SD rats. Methods：The CALP was prepared by reverse-phase evaporation method and the entrapment efficiency，size and zeta potential of CALP were detected. Twelve male SD rats were randomly divided into two groups. The activity of catalase was assayed after respectively intravenous inject－ing CALP and free catalase（CAT） in two groups. The pharmacokinetic parameters were calculated by software DAS 2.1.1，then the bioequivalenee was judged. Results：The entrapment efficiency of CALP was （53.72±1.67）%. The average particle size was （405.40 ± 21.89） nm，and zeta potential was （-15.7±3.22） mV. AUC0-t of CALP and CAT were （203.22±11.75） U（ml·h） and （50.92± 3.51） U（ml·h），Cmax of CALP and CAT were （70.79±1.33） U/ml and （51.48 ± 2.78） U/ml. Tmax of CALP and CAT were （0.58± 0.14） h and （0.17±0.00） h. The 90% confidential intervals of AUC0-t，AUC0-∞ and Cmax of tested formulation were 133.8%-140.1%，132.3%-146.7%，104.7%-107.5%，respectively. Based on analysis of variance and two-sided t-test，lnAUC and lnCmax differed statisti－cally（P<0.05），while Tmax did not differ statistically（P >0.05） between CALP and CAT. The relative bioavailability of CALP was （399.1±23.1）%. Conclusion：CALP improves the bioavailability of catalase. CALP and CAT are not bioequivalent.