当归多糖铁复合物在缺铁性贫血大鼠与正常大鼠体内药动学比较研究

In vivo pharmacokinetic comparison of Angelica sinensis polysaccharide-iron complex in iron-deficiency anemia rats and normal rats

目的比较当归多糖铁复合物(APIC)在缺铁性贫血大鼠与正常大鼠体内的药动学差异,为优化临床给药方案提供参考。方法采用低铁饲料并辅以定期放血法建立缺铁性贫血模型,缺铁性贫血大鼠与正常大鼠分别随机分为APIC低、中、高剂量(5.83、8.75、17.5 mg/kg)组,ig给药,以原子吸收法测定各时间点血清铁浓度,用DAS 2.0软件求算药动学参数,并采用SPSS 13.0软件对同剂量组的缺铁性贫血大鼠和正常大鼠的主要药动学参数进行t检验。结果 APIC在两种不同生理状况下大鼠的药动学过程均符合二室模型,3个剂量组的缺铁性贫血大鼠的血清铁浓度在4 h以后均显著高于健康大鼠,3个剂量组的CL/Ft、1/2β与正常组均有显著差异(P<0.05),但只有高剂量组的t1/2α与正常组有显著差异。结论 APIC在缺铁性贫血大鼠与正常大鼠体内的药动学存在显著差异,并且这种差异与剂量有一定的关系。

Objective To study the pharmacokinetic differences of Angelica sinensis polysaccharide-iron complex（APIC） in iron-deficiency anemia（IDA） rats and normal rats.Methods The IDA model rats were established by feeding iron-deficiency diet and periodic bleeding,IDA rats and normal rats were randomly devided into three groups,respectively.In APIC low,medium,and high（5.83,8.75,and 17.5 mg/kg） dosage groups,serum iron concentration was assayed by atomic absorption spectrometry after ig administration of APIC,the pharmacokinetic parameters were analyzed by DAS 2.0 software.The statistical test was carried out by SPSS 13.0 to compare the main pharmacokinetic parameters（t-test） between IDA rats and normal rats of the same dosage. Results The concentration-time curves of APIC in all groups were fitted to two-compartment open model.Marked differences of iron concentration in serum were found 4 h after administration between IDA rats and normal rats,the serum iron concentration in IDA rats was significantly higher than that in normal rats（P0.05）.In low,medium,and high dosage groups t1/2β of the IDA rats was significantly longer than that of the normal rats,but there was marked difference of t1/2α only in high dosage,CL/F of the IDA rats was significantly lower than that of the rats（P0.05）.Conclusion Data indicates there are significant differences in APIC pharmacokinetics between IDA rats and normal rats,and the differences have a little relationship on the dosage.