Prodrugs are molecules with little or no pharmacological activity that are converted to the active parent drug in vivo by enzymatic or chemical reactions or by a combination of the two. Prodrugs have evolved from being serendipitously discovered or used as a salvage effort to being intentionally designed. Such efforts can avoid drug development challenges that limit formulation options or result in unacceptable biopharmaceutical or pharmacokinetic performance, or poor targeting. In the past 10 years, the US Food and Drug Administration has approved at least 30 prodrugs, which accounts for more than 12% of all approved small-molecule new chemical entities. In this Review, we highlight prodrug design strategies for improved formulation and pharmacokinetic and targeting properties, with a focus on the most recently marketed prodrugs. We also discuss preclinical and clinical challenges and considerations in prodrug design and development.

前药是具有很少或没有药理活性的分子，其通过酶促或化学反应或通过两者的结合在体内转化为活性母体药物。前药已经从偶然发现或用作抢救工作演变为有意设计。这样的努力可以避免药物开发方面的挑战，这些挑战限制了制剂的选择或导致了不可接受的生物药物或药代动力学性能，或者靶向性差。在过去的十年中，美国食品药品监督管理局已经批准了至少30种前药，占所有批准的小分子新化学实体的12％以上。在本综述中，我们重点介绍了用于改善配方，药代动力学和靶向特性的前药设计策略，重点是最新上市的前药。