摘要
目的研究水飞蓟滨对大鼠体内伊马替尼药动学特征的影响。方法 20只♂SD大鼠随机分成2组,Ⅰ组按10 mg·kg^(-1)的剂量灌胃给予5 g·L^(-1)水飞蓟滨,Ⅱ组给予相同量的玉米油。1 h后2组大鼠按50mg·kg^(-1)的剂量灌胃给予5 g·L^(-1)伊马替尼。Ⅰ组和Ⅱ组分别在给药前和给药后0.5、1、2、3、4、6、8、12、24、36、48h时间点尾静脉采血。用HPLC法检测血浆中伊马替尼的浓度,并用DAS计算药动学参数。结果经灌胃给药后,伊马替尼在大鼠体内符合二室模型。Ⅰ、Ⅱ组血浆伊马替尼ρ_(max)分别为(11.77±1.98)和(14.68±2.55)m8·L^(-1),p_(max)分别为(3.00±0.68)和(3.30±0.68)h,AUC_(0→48)分别为(126.24±27.76)和(174.89±34.87)mg·h·L^(-1),AUC_(0→∞)分别为(128.43±27.74)和(178.07±35.46)mg·h·L^(-1),t_1/2α分别为(2.40±0.84)和(4.45±2.52)h,t_(1/2β)分别为(7.82±0.87)和(8.72±1.16)h。Ⅱ组伊马替尼的p_(max)比Ⅰ组增加了24.76%,AUC_(0→48)增加了38.54%,AUC_(0→∞)增加了38.65%,t_(1/2)相对延长。结论水飞蓟滨能增加伊马替尼的ρ_(max)和AUC,延长其t_(1/2),从而影响伊马替尼的代谢。
AIM To study the effect of silybin on the pharmacokinetic characteristics of imafinib in rats. METH- ODS Twenty male SD rats were divided at random into group I and group Ⅱ . Group I was given a single dose of 5 g· L- 1 silybin with intragastrie administration. Group Ⅱwas given the same amount of corn oil. Then 2 groups were given a single dose of 5 g· L-l imatinib with intragastric administration after 1 h. Blood samples were collected from the tail vein before administration and at 0.5,1,2,3,4,6,8,12,24,36 and 48 h points after irnatinib administration. The concentra- tion of imatinib in plasma was detected by HPLC method. The pharmacokinetic parameters were analyzed by DAS pro- gram. RESULTS After imatinib administration, imatinib was fitted to the two-compartment model in rats. The main pharmacokinetic parameters of group I and group II were as follows respectively： Pm~ were （11.77 ± 1.98） and （ 14.68 ± 2.55）mg · L- l, tmax were （ 3.00 ± 0.68） and （ 3.30 ± 0.68） h, AUC0→48 were （ 126.24 ± 27.76） and （ 174.89 ± 34.87） mg· h· L- 1, AUC0→∞ were（ 128.43 ± 27.74） and（ 178.07 ± 35.46） mg· h· L- 1, t1/2α were（2.40 ± 0.84） and（4.45 ± 2.52）h,and t1/2β were（7.82 ± 0.87） and（8.72 ± 1.16）h. When silybin and imatinib were co-ad- ministered, imatinib ρmax increased by 24.76%, AUC0→48 and AUC0→∞ increaed by 38.54% and 38.65 % respectively, and t1/2 were relatively extended. CONCLUSION Silybin could increase the p,~, and AUC of imatinib and extend the t1/2 of imatinib, then could effect the metabolism of imatinib in rots.
出处
《中国临床药学杂志》
CAS
2013年第1期19-22,共4页
Chinese Journal of Clinical Pharmacy
