阿苯达唑纳米球大鼠体内药动学

Study on pharmacokinetics of albendazole nanospheres in rats in vivo

目的研究阿苯达唑聚氰基丙烯酸正丁酯纳米球在大鼠体内的药动学。方法采用RP-HPLC,以甲苯咪唑(MBZ)为内标测定大鼠灌胃给予阿苯达唑混悬液和阿苯达唑纳米球后血浆中的阿苯达唑,阿苯达唑亚砜(ABZSX),阿苯达唑砜(ABZSN)的浓度:色谱条件为十八烷基硅胶填充柱;流速:0.9 mL·min-1;柱温:室温;流动相:乙腈-0.25 mol·L-1醋酸钠缓冲液(pH 5.0) (45:55),计算药动学参数。结果在血浆检测中阿苯达唑的浓度很低或几乎没有检测到。大鼠灌胃给阿苯达唑纳米球后, ABZSX tmax为(4.917±1.88)h,t1/2β为(35.47±2.94)h,相对生物利用度为320.5%.ABZSN的tmax为(6.59±1.97)h,相对生物利用度为180.9%。结论动物口服阿苯达唑纳米球后,增加药物的胃肠道吸收,延长代谢产物ABZSX和ABZSN在体内的驻留时间。

OBJECTIVE To study the pharmacokinetics and bioavailability of albendazole nanospheres in rats by ig administration.METHODS Plasma concentrations of albendazole, albendazole sulphoxide and albendazole sulphone were determined using RP-HPLC method. The chromatographic conditions were a reversed-phase column using acetonitrile-0.25 mol·L^-1 sodium acetate （45：55） as the mobile phase at a flow rate of 0.9 mL·min^-1. The separation was performed at room temperature, and detection wavelength was at 292 nm. The injection volume was 20 μL. Pharmacokintic parameters were calculated. The relative bioavailability was evaluated. RESULTS The plasma concentration-time curves of albendazole sulphoxide （ABZSX） and albendazole sulphone （ABZSN） were fitted to a two-compartment open model. The pharmacokintic parameters of albendazole sulphoxide were as follows ： peak time （ tmax ） （4.92 ±1.88 ） h, clearce （ CL ） （ 0.18 ± 0.038 ） mg·h^-1/ （mg·L^-1）, the hag life of elimination（ t 1/2β） （35.47 ± 2.94）h. There were significant differences from the parameters after the oral administration of albendazole suspension. The relative bioavailability of albendazole sulphoxide was 320.5 %. The parameters of albendazole sulphone peak time （tmax） was （6.59 ± 1.97）h.The relative bioavailability of albendazole sulphone was 180.9% .CONCLUSION Nanospheres increase the gastrointestinal absorption, prolong the residence time of abendazole sulphoxide and sulphone in blood after oral administration. So it improves the bioavailability. The new dosage form is provided for the treatment of echinococcosis.