水溶性水飞蓟素对大鼠体内卡马西平药动学的影响研究

Effects of Water-soluble Silymarin on the Pharmacokinetics of Carbamazepine in Rats

目的:研究水溶性水飞蓟素对大鼠体内卡马西平(CBZ)药动学的影响。方法:取18只大鼠随机均分为对照组(生理氯化钠溶液)、水溶性水飞蓟素普通剂量(50 mg/kg)组、水溶性水飞蓟素高剂量(100 mg/kg)组,灌胃给予相应药物,每日1次,连续给药7 d,末次给药1 h后所有大鼠灌胃给予CBZ 50 mg/kg。分别于给药前及给予CBZ后0.5、1、1.5、2、4、6、8、10、12 h眼眶取血,以地西泮为内标,以高效液相色谱法测定血浆中CBZ及其代谢产物10,11-环氧卡马西平(ECBZ)的浓度,并利用Win Nolin 5.2药动学软件计算药动学参数。结果:与对照组比较,水溶性水飞蓟素普通剂量组和水溶性水飞蓟素高剂量组大鼠体内CBZ的Ka明显增加[(0.31±0.22)vs.(2.66±3.12)、(5.26±4.58)h-1,P<0.05],ECBZ的AUC0-12 h[(53.87±7.31)vs.(70.65±12.79)、(68.44±4.62)mg·h/L,P<0.05]、cmax[(7.20±0.87)vs.(8.82±0.54)、(8.19±0.38)mg/L,P<0.05]明显增加,其余药动学参数比较差异无统计学意义。结论:水溶性水飞蓟素连续服用可促进CBZ在大鼠体内的吸收,同时有促进CBZ体内代谢的趋势,临床上两者合用时应注意潜在的药物相互作用。

OBJECTIVE： To study the effects of water-soluble silymarin on the pharmacokinetics of carbamazepine （CBZ） in rats. METHODS： 18 rats were randomly divided into control group （NaC1 solution）, water-soluble silymarin common-dose group （50 mg/kg） and water-soluble silymarin high-dose group （100 mg/kg）, respectively. They were given relevant medicine once a day for consecutive 7 d. All rats were given CBZ 50 mg/kg intragastrically 1 h after last administration. The orbital blood samples were collected before medication and 0.5, 1, 1.5, 2, 4, 6, 8, 10 and 12 h after CBZ therapy. Plasma concentration of CBZ and its metabolite carbamazepine 10, 11-Epoxide （ECBZ） were determined by HPLC using diazepam as internal standard. Pharmacokinetic parameters were calculated with WinNolin 5.2 pharmacokinetic software. RESULTS ： Compared with control group, K, of CBZ increased significantly [（0.31 ± 0.22） vs.（2.66 ± 3.12）, （5.26 ± 4.58） h 1,P〈0.05], AUC0-2 h [（53.87 ± 7.31） vs. （70.65 ±12.79）, （68.44 ±4.62） rag.h/L, P〈0.05] and [（7.20±0.87） vs. （8.82± 0.54）, （8.19 ± 0.38） mg/L,P〈0.05] of ECBZ increased signif icantly in water-soluble silymarin common-dose group and water-soluble silymarin high-dose group; there was no statistical significant difference in other phannacokinetic parameters. CONCLUSIONS： Consecutive administration of water-soluble silymarin may promote the absorption of CBZ and the metabolism of it in rats. Great importance should be attached to potential drug interaction of water-soluble silymarin and CBZ.