Chongqing Research Center for Pharmaceutical Engineering, Chongqing Medical University, Chongqing, China.
Department of Thoracic Surgery, Daping Hospital of Army Medical University, PLA, Chongqing, China.
Drug Metab Rev. 2020 Feb;52(1):19-43. doi: 10.1080/03602532.2020.1714646. Epub 2020 Jan 26.
Today, it is very challenging to develop new active pharmaceutical ingredients. Developing good preparations of well-recognized natural medicines is certainly a practical and economic strategy. Low-solubility, low-permeability natural medicines (LLNMs) possess valuable advantages such as effectiveness, relative low cost and low toxicity, which is shown by the presence of popular products on the market. Understanding the metabolic and pharmacokinetic characteristics of LLNMs contributes to overcoming their associated problems, such as low absorption and low bioavailability. In this review, the structure-based metabolic reactions of LLNMs and related enzymatic systems, cellular and bodily pharmacological effects and metabolic influences, drug-drug interactions involved in metabolism and microenvironmental changes, and pharmacokinetics and dose-dependent/linear pharmacokinetic models are comprehensively evaluated. This review suggests that better pharmacological activity and pharmacokinetic behaviors may be achieved by modifying the metabolism through using nanotechnology and nanosystem in combination with the suitable administration route and dosage. It is noteworthy that novel nanosystems, such as triggered-release liposomes, nucleic acid polymer nanosystems and PEGylated dendrimers, in addition to prodrug and intestinal penetration enhancer, demonstrate encouraging performance. Insights into the metabolic and pharmacokinetic characteristics of LLNMs may help pharmacists to identify new LLNM formulations with high bioavailability and amazing efficacy and help physicians carry out LLNM-based precision medicine and individualized therapies.
如今，开发新的活性药物成分极具挑战性。开发广为人知的天然药物的优质制剂无疑是一种实用且经济的策略。低溶解度、低渗透性天然药物（LLNMs）具有有效性、相对低成本和低毒性等优势，这一点在市场上的热门产品中得到了体现。了解 LLNMs 的代谢和药代动力学特征有助于克服其相关问题，如低吸收和低生物利用度。在这篇综述中，全面评估了基于结构的 LLNMs 的代谢反应及其相关酶系统、细胞和全身药理学效应和代谢影响、涉及代谢和微环境变化的药物相互作用以及药代动力学和剂量依赖性/线性药代动力学模型。这篇综述表明，通过使用纳米技术和纳米系统结合合适的给药途径和剂量来修饰代谢，可以实现更好的药理活性和药代动力学行为。值得注意的是，新型纳米系统，如触发释放脂质体、核酸聚合物纳米系统和聚乙二醇化树枝状大分子，除了前药和肠道渗透增强剂外，还表现出令人鼓舞的性能。对 LLNMs 代谢和药代动力学特征的深入了解可能有助于药剂师识别具有高生物利用度和惊人疗效的新型 LLNM 制剂，并帮助医生开展基于 LLNM 的精准医学和个体化治疗。
