酮康唑对奥拉西坦在大鼠体内药代动力学的影响

目的建立测定大鼠血浆中奥拉西坦含量的高效液相色谱法,研究酮康唑对奥拉西坦在大鼠体内药代动力学的影响。方法色谱柱为DiamonsilRPC18柱(250mm×4.6mm,5μm),流动相为乙腈-水(3.2:96.8),流速为0.8mL/min,检测波长210nm,柱温40℃,进样量20μL。试验组大鼠连续灌胃给予酮康唑(50mg/kg,每日1次)7d后,单次灌胃给予奥拉西坦(200mg/kg),测定奥拉西坦血药浓度,计算药代动力学参数,并与单次灌胃给予奥拉西坦(200mg/kg)的对照组进行比较。结果奥拉西坦标准曲线方程为Y=0.0217X+0.1058(r=0.9992,n=7),质量浓度线性范围为2～100mg/L;低、中、高3种质量浓度的方法回收率分别为(102.25±8.51)%,(96.29±2.76)%和(98.14±1.62)%,日内及日间精密度的RSD均小于5.42%。对照组与试验组主要药代动力学参数,半衰期(t1/2)分别为(2.807±0.8751)h和(3.231±1.019)h,峰浓度(Cmax)分别为(52.80±16.94)mg/L和(47.33±8.317)mg/L,0～12h药时曲线下面积(AUC0-12h)分别为(257.2±77.84)mg.h/L和(258.9±67.30)mg.h/L,组间比较无显著性差异。结论酮康唑对大鼠体内奥拉西坦的药代动力学无显著影响。

Effects of Ketoconazole on Pharmacokinetics in Vivo of Oxiracetam in Rats

Objective To establish a HPLC method for the determination of the oxiracetam content in plasm of rats,and to study the influence of ketoconazole on the oxiracetam pharmacokinetics in vivo in rats. Methods The chromatographic column was the Diamonsil RP C1 column（250 mmx4.6 mm,5 um） with the mobile phase of acetonitrile-water（3.2：96.8） at the flow rate of 0.8 mL/min. The detection wavelength was set at 210 nm and the column temperature was 40 ~C. The injected volume was 20 p.L. The rats in the test group were given ketoconazole （50 mg/kg,once daily） by continuous intragastric gavage for 7 d. Then,the single dose of oxiracetam （200 mg/kg） was given to each rat in the test group. The plasm concentration of oxiracetam was determined and the pharmacokinetic parameters were calculated, which was compared with that of the control group after intragastric gavage of oxiracetam （200 mg/kg） alone. Results The standard curve equation of oxiracetam was Y=0. 021 7X ＋0. 105 8（ r =0. 999 2, n--7） with the mass concentra- tion linear range of 2- 100 mg/L. The recovery rates of the low, middle and high mass concentrations were （102.25 ＋8.51）% , （96.29 ＋ 2.76）% and （98.14 ＋ 1.62）% , respectively, and RSD of intra - day and inter - day precisions were less then 5.42%. The main pharmacokinetic parameters of the control group and the test group were t （2. 807±0.875 1） h and （3.231 ±1.019） h, Cmax = （52. 80 ±16. 94） mg/L and （47.33±8.317） mg/L, AUCo-lzh=（257.2±77.84） mg/（h L） and （258.9＋67.30） mg/（h L）, respectively, there was no statistical differenee between the two groups. Conclusion Ketoconazole has no signifieant influence on the oharmacokinetics in vivo of oxiracetam in rats.