Gomez-Orellana Isabel
Emisphere Technologies, Inc. 765 Old Saw Mill River Road, Tarrytown, NY 10591, USA.
Expert Opin Drug Deliv. 2005 May;2(3):419-33. doi: 10.1517/17425247.2.3.419.
Efforts to improve oral drug bioavailability have grown in parallel with the pharmaceutical industry. As the number and chemical diversity of drugs has increased, new strategies have been required to develop orally active therapeutics. The past two decades have been characterised by an increased understanding of the causes of low bioavailability and a great deal of innovation in oral drug delivery technologies, marked by an unprecedented growth of the drug delivery industry. The advent of biotechnology and consequent proliferation of biopharmaceuticals have brought new challenges to the drug delivery field. In spite of the difficulties associated with developing oral forms of this type of therapeutics, significant progress has been made in the past few years, with some oral proteins, peptides and other macromolecules currently advancing through clinical trials. This article reviews the approaches that have been successfully applied to improve oral drug bioavailability, primarily, prodrug strategies, lead optimisation through medicinal chemistry and formulation design. Specific strategies to improve the oral bioavailability of biopharmaceuticals are also discussed.
提高口服药物生物利用度的努力与制药行业同步发展。随着药物数量和化学多样性的增加，开发口服活性治疗药物需要新的策略。在过去的二十年中，人们对低生物利用度的原因有了更多的了解，口服药物递送技术也有了大量创新，药物递送行业呈现出前所未有的增长。生物技术的出现以及随之而来的生物制药的激增给药物递送领域带来了新的挑战。尽管开发这类治疗药物的口服剂型存在困难，但在过去几年中仍取得了重大进展，目前一些口服蛋白质、肽和其他大分子正在进行临床试验。本文综述了已成功应用于提高口服药物生物利用度的方法，主要是前药策略、通过药物化学进行先导优化和制剂设计。还讨论了提高生物制药口服生物利用度的具体策略。
