Porter Christopher J H, Trevaskis Natalie L, Charman William N
Department of Pharmaceutics, Victorian College of Pharmacy, Monash University, Parkville campus, 381 Royal Parade, Parkville, Victoria 3052, Australia.
Nat Rev Drug Discov. 2007 Mar;6(3):231-48. doi: 10.1038/nrd2197.
Highly potent, but poorly water-soluble, drug candidates are common outcomes of contemporary drug discovery programmes and present a number of challenges to drug development - most notably, the issue of reduced systemic exposure after oral administration. However, it is increasingly apparent that formulations containing natural and/or synthetic lipids present a viable means for enhancing the oral bioavailability of some poorly water-soluble, highly lipophilic drugs. This Review details the mechanisms by which lipids and lipidic excipients affect the oral absorption of lipophilic drugs and provides a perspective on the possible future applications of lipid-based delivery systems. Particular emphasis has been placed on the capacity of lipids to enhance drug solubilization in the intestinal milieu, recruit intestinal lymphatic drug transport (and thereby reduce first-pass drug metabolism) and alter enterocyte-based drug transport and disposition.
高效但水溶性差的候选药物是当代药物研发项目的常见成果，给药物开发带来了诸多挑战——最显著的是口服给药后全身暴露减少的问题。然而，越来越明显的是，含有天然和/或合成脂质的制剂是提高某些水溶性差、亲脂性高的药物口服生物利用度的可行方法。本综述详细阐述了脂质和脂质辅料影响亲脂性药物口服吸收的机制，并对基于脂质的递送系统未来可能的应用提供了一个观点。特别强调了脂质在增强药物在肠道环境中的溶解能力、促进肠道淋巴药物转运（从而减少首过药物代谢）以及改变基于肠上皮细胞的药物转运和处置方面的能力。
