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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。
Objective To study the effect of silymarin on the pharmacokinetics of imatinib in rats. Methods Twenty male SD rats were randomly divided into 2 groups. Group Ⅰ was treated with 5 g · L -1 silybin at a dose of 10 mg · kg -1. Group Ⅱ was given the same amount of corn oil. After 1 h, the rats in two groups were administered with 5 g · L -1 imatinib at a dose of 50 mg · kg -1. Group Ⅰ and group Ⅱ, respectively, before administration and after administration of 0.5,1,2,3,4,6,8,12,24,36,48 h time tail vein blood collection. The concentration of imatinib in plasma was detected by HPLC and the pharmacokinetic parameters were calculated by DAS. Results After intragastric administration, imatinib conformed to the two-compartment model in rats. The ρ max of imatinib in group Ⅰ and Ⅱ were (11.77 ± 1.98) and (14.68 ± 2.55) m8 · L -1, and the max were 3.00 ± 0.68 and 3.30 ± 0.68) h, AUC_ (0 → 48) were (126.24 ± 27.76) and (174.89 ± 34.87) mg · h · L -1, respectively, and AUC_ (0 → ∞) were (128.43 ± 27.74) and (2.40 ± 0.84) and (4.45 ± 2.52) h, respectively, and the values of t 1 / 2β were (7.82 ± 0.87) and (8.72 ± 1.16 h. The p_ (max) of imatinib in group Ⅱ increased 24.76%, AUC_ (0 → 48) increased 38.54%, AUC_ (0 → ∞) increased 38.65% and t_ (1/2) increased relatively. Conclusion Silybin can increase ρ_ (max) and AUC of imatinib and extend its t_ (1/2), thus affecting the metabolism of imatinib.