“Cocktail”探针药物法评价苦碟子注射液对大鼠CYP450酶活性的影响

Evaluation of Kudiezi Injection on CYP450 Enzyme Activity of SD Rats by Cocktail Probe Drugs

目的探究苦碟子注射液对大鼠细胞色素P450酶亚型CYP3A4和CYP2E1酶活性的影响。方法将SD雄性大鼠随机分成4组(n=8),分苦碟子注射液高剂量组,临床等效剂量组,阳性药组(苯巴比妥钠),生理盐水组,给药2周后,在第15天早上尾静脉注射给予氯唑沙宗(10mg·kg^(-1))和氨苯砜(10mg·kg^(-1))。用HPLC法测定大鼠血浆探针药物浓度,获得各探针药物的药代动力学参数评价苦蝶子注射液对大鼠CYP3A4、CYP2E1活性的影响。结果持续腹腔注射苦碟子注射液14d后,和空白组比较,氨苯砜的血药浓度及药动学参数变化无统计学差异(P>0.05),药物对大鼠CYP3A4的活性水平影响较小;氯唑沙宗的AUC0-t和AUC0-∞减小,t1/2降低,CL增大,差异均有统计学意义(P<0.05)。苦碟子注射液临床给药剂量组和高剂量组大鼠CYP2E1的活性水平均高于对照组,差异有统计学意义(P<0.05)。结论苦碟子注射液能较强的诱导大鼠肝药酶CYP2E1活性,而对CYP3A4活性影响不大,但与阳性药(苯巴比妥)的诱导强度相比较弱。

OBJECTIVE To evaluate the effect of Kudiezi Injection on CYP450 enzyme activity by cocktail probe drugs in male SD rats. METHODS Male SD rats were randomly divided into four groups （each n = 5） ,inclu- ding high-dose group, low-dose group of Kudiezi Injection, positive control group （Phenobarbital）, blank control group. A series of cocktail probe drugs including dapsone（ 10mg· kg-1） , and chlorzoxazone（ 10mg · kg-1） were re- spectively infused into abdominal cavity of rats in the morning of d15 as the probes of cytochrome P450（CYP） en- zyme isoform of CYP3A4 and CYP2E1 after multiple dosing of Kudiezi Injection. The plasma concentrations of the two probes were determined by HPLC and their corresponding pharmacokinetic parameters were calculated to evalu- ate the possible effect of Kudiezi Injection extracts on CYP450 enzyme activity. RESULTS AUC0-t,AUC0-∞ and the concentration of chlorzoxazone were decreased significantly （P 〈 0. 05 ） and the CL was increased in rats after Kudie- zi Injection for 14 consecutive days, in comparing with the blank control group. The activities of the CYP2E1 in the rats received Kudiezi Injection were significantly enhanced （P 〈 0. 05 ）. CONCLUSION Kudiezi Injection had ob- vious induction on CYP2E1 in rats.