辛伐他汀自微乳化释药系统在Beagle犬体内的药动学特征

Pharmacokinetics of self-microemulsifying drug delivery system of simvastatin in Beagle dogs

目的研究辛伐他汀自微乳化释药系统(SV-SMEDDS)在Beagle犬体内的药动学特征。方法采用Waters OASIS○RHLB固相萃取小柱提取样品,RP-HPLC法测定Beagle犬血浆药物浓度。双周期交叉实验设计,与辛伐他汀混悬液(SV-Sus)比较,考察单剂量灌胃给予含辛伐他汀40 mg后SV-SMEDDS的体内药动学。结果SV-SMEDDS与SV-Sus在犬体内的药动学均符合二室模型;tmax分别为(0.84±0.26)和(0.99±0.32)h,ρmax分别为(39.73±9.11)和(28.54±7.76)μg.L-1;SV-SMEDDS相对生物利用度为184.84%(以AUC0→∞计)。结论自微乳化释药系统可以提高辛伐他汀的生物利用度。

AIM To evaluate the pharmacokinetics of self-mieroemulsifying drug delivery system of simvastatin （SV-SMEDDS） in Beagle dogs. METHODS Plasma simvastatin was determined by RP-HPLC with solid-phase extraction using Waters OASIS^＊HLB cartridge. The pharmacokinetics of SV-SMEDDS was evaluated after a single oral dose of 40 mg of simvastain in a two-period crossover experiment design compared with simvastafin suspension （SV-Sus）. RESULTS The pharmacokinetics of both SV-SMEDDS and SV-Sus fitted to two-compartment model. The tmax were （0.84±0.26） and（0.99 ± 0.32）h for SV-SMEDDS and SV-Sus respectively, and ρmax were （39.73 ±9.11） and （28.54 ±7.76）μg·L^-1 respectively. SV-SMEDDS showed a relative bioavailability of 184.84%. CONCLUSION SMEDDS is able to increase the absorbance and bioavailability of simvastatin.