氟伐他汀对厄贝沙坦药代动力学的影响研究

目的探讨低剂量（10 mg/kg）和高剂量（50 mg/kg）氟伐他汀分别诱导3 d对新西兰大白兔体内厄贝沙坦药代动力学的影响。方法将18只新西兰大白兔随机分为对照组（以2%羧甲基纤维素溶液为对照,单用厄贝沙坦50mg/kg）、氟伐他汀低剂量诱导组和氟伐他汀高剂量诱导组。采用高效液相色谱一荧光法测定血药浓度,DAS 3.0软件进行数据处理,计算药代动力学参数,测定峰浓度（c_（max））和达峰时间（T_（max））。结果与对照组比较,氟伐他汀低剂量诱导组厄贝沙坦在新西兰大白兔体内的主要药代动力学参数如药时曲线下面积（AUC）、表观清除率（CL）、C_（max）、一半衰期（t_（1/2））等无显著性差异;而氟伐他汀高剂量诱导组的主要药代动力学参数AUC_（（0-36））、AUC_（（10-∞））、MRT_（10-∞）虽有变化,但均无统计学差异t_（1/2）和MRT_（（0-36））显著延长（P〈0.05）,且CL显著降低（P〈0.05）。结论氟伐他汀低剂量诱导对新西兰大白兔体内厄贝沙坦的药代动力学无影响,氟伐他汀高剂量诱导显著影响新西兰大白兔体内厄贝沙坦的药代动力学。

Influence of Fluvastatin on Pharmacokinetics of Irbesartan

Objective To investigate the influence of fluvastatin on the in vivo pharmacokinetics of irbesartan after low dose （10 mg/kg） and high dose （50 mg/kg） of fluvastatin for 3 d induction in New Zealand white rabbits. Methods Eighteen New Zealand white rab- bits were randomly divided into 3 groups： control group（2% earboxymethyl cellulose solution as control, single irbesartan 50 mg/kg）, flu- vastatin low dose（10 mg/kg） group and fluvastatin high dose（50 mg/kg） group. The concentrations of irbesartan were detected by the HPLC-fluorescence method. The detection results were analyzed with the DAS 3.0 software for calculating the pharmacokinetic parameters. Cmax and Tmax were detected. Results Compared with the control group, the in vivo irbesartan pharmacokinetic parameters of AUC, CL, Cmax t1/2, etc. in the fluvastatin low dose group had no significant differences; while the irbesartan pharmacokinetic parame- ters such as AUC（0-36）, AUC（0-∞ ）, MRT（0-∞ ） had change, but without statistically significant differences, t1/2 and MRT（0-36） were signifi- cantly prolonged（ P 〈 0.05 ） and CL was decreased significantly（ P 〈 0. 05）. Conclusion The fluvastatin low dose induction has no sig- nificant influence on the in vivo pharmacokinetics of irbesartan, but the fluvastatin high dose induction significantly affects the in vivo pharmacokinetics of irbesartan.