摘要
目的:建立快速、简单测定Beagle犬血浆中川芎嗪浓度的HPLC方法,研究丹参川芎嗪注射液中的川芎嗪在健康Beagle犬体内的药动学特征。方法:6只Beagle犬雌雄各半,以盐酸川芎嗪的剂量计,分别以40 mg·kg-1单次静注,以20 mg·kg-1多次静注丹参川芎嗪注射液,进行丹参川芎嗪注射液中川芎嗪的非临床药动学研究。结果:本方法血浆中川芎嗪线性范围为0.099 2~99.20μg·ml-1(r=0.997 0);日内及日间精密度RSD均小于11%。以40 mg·kg-1单次静注丹参川芎嗪注射液后,川芎嗪的t1/2为(3.6±3.0)h;Cmax为(31.1±5.8)μg·ml-1;AUC0→∞为(1.81±0.47)μg·min·L-1。以20 mg·kg-1多次静注丹参川芎嗪注射液后,川芎嗪的t1/2为(12.1±8.6)h;Cmax为(8.7±4.4)μg·ml-1;AUC0→∞为(0.59±0.12)μg·min·L-1。结论:本方法简单、快速、重复性好,适用于快速测定Beagle犬血浆中川芎嗪浓度。Beagle犬单次给药和多次给药静脉注射给予丹参川芎嗪注射液后,川芎嗪在体内的处置均符合三室模型,由多次给药试验结果可得出结论丹参川芎嗪注射液中川芎嗪在Beagle犬体内没有表现出蓄积现象,单次给药给予相同剂量时性别对川芎嗪体内过程无影响。
OBJECTIVE To set up a HPLC method to determine the concentration of tigustrazine in Beagle dog＇s plasma and study the pharmacokinetic characters of ligustrazine in Beagle dogs after intravenous （IV） injection of Salviae miltiorrhiza ligustrazine hydrochloride injection. METHODS 6 Beagle dogs, body weight range from 8 - 11 kg, were chosen to take part in the experiment, with half males and half females. The Beagle dogs were administered with single dose of 40 mg. kg- 1 of ligus- trazine hydrochloride and multiple dose of 20 mg.kg 1 of ligustrazine hydrochloride by IV injection, to study the non-clinical pharmacokinetics of ligustrazine in Salviae miltiorrhiza ligustrazine hydrochloride injection. RESULTS The linear range of li- gustrazine in Beagle dog plasma was 0. 099 2 - 99. 20 txg.ml ＇ （r = 0. 997 0）. The intra-day and inter-day RSD were tess than 11%. After receiving single doses of Salviae miltiorrhiza ligustrazine hydrochloride injection, A/2 was（3.6 ＋ 3. 0）h; Cmax was （31. 1 ＋ 5. 8） /~g-ml-~ ;AUC0--,-oo was （1.81 ＋ 0. 47） /lg.min-L 1. After receiving multiple doses of Salviae miltiorrhiza li- gustrazine hydrochloride injection, t~/2 was （12.1 ＋8. 6） h; Cr=x was （8. 7 ＋ 4. 4） ~g.ml-1 ; AUG^-~ was （0. 59 ＋ 0. 12） /ag. min.L-~. CONCLUSION The established HPLC method is simple, rapid and reproducible. It could be used for determination of the concentration of ligustrazine in Beagle dog plasma. The pharmacokinetic profile of ligustrazine in Beagle dogs after single i.v. at the dose of 40 mg. kg- 1 and multiple i. v. at the dose of 20 mg. kg- ~ are both three-compartment model. The results of multiple dose administration show that ligustrazine has no accumulation in Beagle dogs. In addition, the results suggested that gender had no statistic significant effect on the pharmacokinetic process of ligustrazine after IV injection of single dose.
出处
《中国医院药学杂志》
CAS
CSCD
北大核心
2014年第2期98-102,共5页
Chinese Journal of Hospital Pharmacy
关键词
丹参川芎嗪注射液
川芎嗪
高效液相色谱法
药动学
Salviaemiltiorrhiza ligustrazine hydrochloride injection
ligustrazine
HPLC
pharmacokinetics
