Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151 Malianwa North Road, Haidian District, Beijing, 100193, P. R. China.
Key Laboratory for Neurodegenerative Diseases (Capital Medical University), Ministry of Education, Beijing, 100054, China.
Drug Deliv Transl Res. 2017 Oct;7(5):731-737. doi: 10.1007/s13346-017-0402-7.
Due to intestinal cytochrome P450 (CYP450)-mediated metabolism and P-glycoprotein (P-gp) efflux, poor oral bioavailability hinders ginsenoside-Rh1 (Rh1) and ginsenoside-Rh2 (Rh2) from clinical application. In this study, Rh1 and Rh2 were incorporated into two self-microemulsions (SME-1 and SME-2) to improve oral bioavailability. SME-1 contained both CYP450 and P-gp inhibitory excipients while SME-2 only consisted of P-gp inhibitory excipients. Results for release, cellular uptake, transport, and lymph node distribution demonstrated no significant difference between either self-microemulsions in vivo, but were elevated significantly in comparison to the free drug. The pharmaceutical profiles in vivo showed that the bioavailability of Rh1 in SME-1 (33.25%) was significantly higher than that in either SME-2 (21.28%) or free drug (12.92%). There was no significant difference in bioavailability for Rh2 between SME-1 (48.69%) or SME-2 (41.73%), although they both had remarkable increase in comparison to free drug (15.02%). We confirmed that SME containing CYP450 and P-gp inhibitory excipient could distinctively improve the oral availabilities of Rh1 compared to free drug or SME containing P-gp inhibitory excipient. No notable increase was observed between either SME for Rh2, suggesting that Rh2 undergoes P-gp-mediated efflux, but may not undergo distinct CYP450-mediated metabolism.
由于肠道细胞色素 P450（CYP450）介导的代谢和 P 糖蛋白（P-gp）外排，较差的口服生物利用度阻碍了人参皂苷 Rh1（Rh1）和人参皂苷 Rh2（Rh2）的临床应用。在本研究中，将 Rh1 和 Rh2 纳入两种自微乳（SME-1 和 SME-2）中以提高口服生物利用度。SME-1 包含 CYP450 和 P-gp 抑制性赋形剂，而 SME-2 仅包含 P-gp 抑制性赋形剂。体内释放、细胞摄取、转运和淋巴结分布的结果表明，两种自微乳之间没有明显差异，但与游离药物相比，均显著升高。体内药物特征表明，SME-1 中 Rh1 的生物利用度（33.25%）明显高于 SME-2（21.28%）或游离药物（12.92%）。SME-1（48.69%）或 SME-2（41.73%）中 Rh2 的生物利用度之间没有显著差异，尽管与游离药物（15.02%）相比，均有明显增加。我们证实，含有 CYP450 和 P-gp 抑制性赋形剂的 SME 可显著提高 Rh1 的口服生物利用度，优于游离药物或仅含有 P-gp 抑制性赋形剂的 SME。对于 Rh2，两种 SME 之间均未观察到明显增加，表明 Rh2 经历 P-gp 介导的外排，但可能不经历明显的 CYP450 介导的代谢。
