8-十六烷基小檗碱与小檗碱的大鼠药代动力学和组织分布比较研究

Comparative study of pharmacokinetics and tissue distribution of 8-cetylberberine and berberine in rats

高效液相色谱法测定小檗碱(BBR)和8-十六烷基小檗碱(8-BBR-C16)在大鼠血浆及组织中的浓度,比较二者的药代动力学规律和组织分布差异,为8-BBR-C16的机制研究及药物开发提供实验数据。大鼠灌胃80mg·kg-1药物后,在药动学实验结果中,与BBR相比,8-BBR-C16的Cmax、AUC0-t分别是BBR的2.8倍和12.9倍,tl/2由3.61 h延长到11.90 h。在组织分布实验结果中,与BBR相比,8-BBR-C16在各种组织的分布浓度均有显著提高,停滞时间明显延长。其在肺中的药物浓度最高,最高浓度达到3 731.82 ng·g-1。8-BBR-C16经衍生化后,在血浆中Cmax及生物利用度显著提高,体内循环时间延长,组织中的药物分布浓度显著提高,分布比例改变,具有较强的肺靶向性。

The concentrations of berberine（BBR） and 8-cetylberberine（8-BBR-C16） in rat plasma and tissue were determined by RP-HPLC. Both the plasma pharmacokinetics characteristic and tissue distribution differences of BBR and 8-BBR-C16 were compared to provide experimental data for the mechanism research and further drug development. After the oral administrations of BBR and 8-BBR-C16 at the dose of 80 mg·kg^-1 for rats,the pharmacokinetics result showed that compared with BBR,the Cmax and AUC0-t of 8-BBR-C16 increased by 2.8 times and 12.9 times respectively,tl/2 extended from 3.61 h to 11.90 h. The tissue distribution result showed that compared with BBR,the concentration of 8-BBR-C16 in various organizations increased and the retention time extended remarkably. The maximum concentration was achieved in lung and the highest concentration in it was 3 731.82 ng·g^-1. After being derived,the Cmax in plasma and bioavailability of 8-BBR-C16 increased remarkably and the circulation time in vivo extended. The drug concentration in tissue increased remarkably,and the distribution ratio changed too,with strong targeting selection in lung.