食物对大鼠体内尼莫地平药代动力学的影响

Food Effect on Pharmacokinetics of Nimodipine in Rats

目的建立高效液相色谱串联质谱(HPLC-MS/MS)法测定大鼠血浆中尼莫地平的质量浓度,并研究食物对大鼠体内尼莫地平药代动力学的影响。方法将18只雄性SD大鼠随机分成3组,分别于空腹、进食标准餐和进食高脂餐后灌胃尼莫地平20 mg/kg,采用HPLC-MS/MS法测定大鼠血浆中尼莫地平浓度,用Win Nonlin 6.3软件计算主要药代动力学参数。结果大鼠于空腹、进食标准餐和进食高脂餐后灌胃给予尼莫地平的主要药代动力学参数峰浓度(Cmax)分别为(19.19±4.76)ng/m L,(30.14±7.91)ng/m L,(34.39±8.03)ng/m L,达峰时间(Tmax)分别为0.96 h,0.79 h和0.75 h,药时曲线下面积(AUCinf)分别为(94.47±17.24)ng/(m L·h),(139.6±32.9)ng/(m L·h),(148.1±34.2)ng/(m L·h);大鼠进食后给药的药代动力学参数与空腹相比,均有显著性差异(P<0.05),而标准餐组和高脂餐组间的差异无统计学意义。结论进食可显著提高尼莫地平在大鼠体内的吸收速度和程度。

Objective To develop an HPLC-MS/MS method for the determination of nimodipine in rat plasma, and to study the food effect on pharmacokinetics of nimodipine in rats. Methods 18 male SD rats were randomly divided into 3 groups, and were gavaged with nimodipine at a dose of 20 mg/kg under fasting conditions, with a standard meal or with a high-fat meal. The concentrations of nimodipine in rat plasma were analyzed with HPLC -MS/MS system, and WinNonlin 6. 3 software was utilized to perform the pharmacokinetic parameters calculation. Results The mean Cmax, Tmax and AUCinf were (19. 19 ± 4. 76), (30. 14 ± 7. 91) and (34. 39 ± 8. 03) ng/mL, 0. 96, 0. 79 and 0. 75 h, (94. 47 ± 17. 24), (139. 6 ± 32. 9) and (148. 1 ± 34. 2) ng/ (mL· h) under fasting conditions, with a standard meal or with a high-fat meal in rats. Administered with food showed influence on the pharmacokinetics of nimodipine, with Cmax, Tmax and AUCinf significantly increased compared with fasting group ( P < 0. 05 ) , but no significant differences were found be-tween the standard meal and high-fat meal group. Conclusion Administered with food can increase the rate and extent of nimodipine absorption in rats.