奈韦拉平纳米混悬液的制备及大鼠体内药动学研究

Preparation and Pharmacokinetics of Nevirapine Nanosuspensions in Rats

目的:制备奈韦拉平纳米混悬剂,考察其在大鼠口服给药后体内的药动学特征。方法:采用高压均质法制备奈韦拉平纳米混悬剂,以纳米混悬剂粒径分布、Pd I和Zeta电位为指标,考察了奈韦拉平纳米混悬剂的影响因素,并对制得的纳米粒进行表征;采用高效液相色谱法测定大鼠血浆中的奈韦拉平浓度,使用3P97软件计算相应的药动学参数。结果:奈韦拉平纳米混悬液平均粒径为(456.1±72.1)nm,Pd I为(0.441±0.072),Zeta电位为(-24.4±4.7)m V。奈韦拉平混悬液和奈韦拉平纳米混悬剂在大鼠体内的AUC0-12分别为(7.57±0.52)和(11.72±1.83)mg·h·L-1;t1/2分别为(2.45±0.31)和(3.16±0.39)h;Tmax分别为(1.43±0.38)和(1.61±0.32)h;Cmax分别为(1.62±0.42)和(3.15±0.52)mg·L-1。结论:奈韦拉平纳米混悬液能够明显改善大鼠体内奈韦拉平的药动学行为,与奈韦拉平混悬液相比显著提高了药物的生物利用度。

Objective： To prepare nevirapine nanosuspensions （Nev-NS） and study the pharmacokinetics in rats. Methods： Nev- NS was prepared by a high pressure homogenization technology. The panicle size, PDI and Zeta potential of the nanosuspensions were used as the indices to determine the influencing factors in the preparation process. Nevirapine plasma concentration was detected by HPLC and the pharmacokinetic parameters were calculated by 3P97 software. Results： The particle size, PDI and Zeta potential of Nev-NS was （456.1±72.1） nm, 0.441 ±0.072 and （ -24.4±4.7） mV, respectively. AUCo2 of Nev and Nev-NS was （7.57± 0.52） and （11.72±1.83） mg. h. L-1, t was （2.45±0.31） and （3.16 ±0.39） h, T was （1.43 ±0.38） and （1.61 ± 0.32 ） h and C was （ 1.62 ±0.42） and （3.15± 0.52） mg . L -1 , respectively. Conclusion： Nev-NS can improve the pharmacoki- netic behavior of Nev in rats significantly, and obviously enhance the bioavailabilitv when comoared with neviraoine susnensions.