木犀草素在大鼠体内的药动学研究

Pharmacokinetics of Luteolin in Rats

目的建立HPLC-UV方法,研究木犀草素灌胃及腹腔给药后原形药物及结合形药物在大鼠体内的药动学,并测定灌胃给药后大鼠胆汁排泄情况。方法利用HPLC-UV方法,测定大鼠灌胃及腹腔给药20 mg·kg^(-1)后血浆及血浆样品水解后木犀草素浓度。测定灌胃给药后各个时间段胆汁样品水解后木犀草素浓度,计算20 h内胆汁的排泄率。利用DAS计算出主要药代参数。结果木犀草素灌胃给药后,血浆中游离木犀草素的AUC_(0-t),MRT_(0-t),ρ_(max),t_(max)分别为0.212 6 mg·h·L^(-1),4.52 h,0.05 mg·L^(-1),0.25 h;游离与结合形式总和的药代参数分别为12.076 6 mg·h·L^(-1),7.89 h,1.45 mg·L^(-1),8 h。腹腔给药后,血浆游离木犀草素的AUC_(0-t),MRT_(0-t),ρ_(max),t_(max)分别为4.642 1 mg·h·L^(-1),3.81 h,1.71 mg·L^(-1),0.5 h;血浆游离与结合形式的药代参数分别为36.720 9 mg·h·L^(-1),6.98 h,7.755 mg·L^(-1),0.5 h。胆汁样品水解处理后12 h的总排泄量约为给药量的0.87%。胆汁中药物浓度在1～2 h和8～12 h时间段较高。胆汁中药物浓度不随时间而降低。结论建立的HPLC方法可用于木犀草素的药动学研究。木犀草素给药后在体内主要以结合形式存在。口服给药后木犀草素部分以结合形式通过胆汁排泄。

OBJECTIVE To study pharmacokinetics of luteolin in rats after oral and intraperitoneal administration, and to determinate the bile excretion. METHODS Free luteolin and glucuronide-conjugates in plasma and bile were determined after oral or intraperitoneal administration at dosage of 20 mg·kg^-1. Pharmacokinetic parameters were calculated by DAS pharmacokinetic program. RESULTS The AUC0-t, MRT0-t, ρmax,tmax after oral administration were 0. 212 6 mg·h·L^-1,4. 52 h,0. 05 mg·L^-1,0. 25 h for free luteolin and 12.076 6 mg·h·L^-1 ,7.89 h, 1.45 mg·L^-1 , 8 h for total luteolin （ free and conjugates）. After intraperitoneal administration, the AUC0-t ,MRT0-t, ρmax,t max were 4. 642 1 mg·h·L^-1 ,3.81 h, 1.71 mg·L^-1 ,0. 5 h for free and total luteolin and 36. 720 9 mg·h·L^-1 ,6.98 h,7.755 mg·L^-1,0. 5 h for total luteolin respectively. Luteolin in bile concentration were at high level during 1 -2 h and 8 - 12 h, the concentration did not decline with the time, and the bile excretion ration during 12 h was 0. 87%. CONCLUSION The method was suitable for pharmacokinetic study. Luteolin was present mainly as glucuronide conjugates in plasma and bile. Part of luteolin excreted from bile after oral administration.