Pritchard J Fred, Jurima-Romet Malle, Reimer Mark L J, Mortimer Elisabeth, Rolfe Brenda, Cayen Mitchell N
MDS Pharma Services, 3504 Proprietor Way, Raleigh, North Carolina 27612, USA.
Nat Rev Drug Discov. 2003 Jul;2(7):542-53. doi: 10.1038/nrd1131.
Drug development is a risky business. Success or failure often depends on selecting one or two molecules for development from many choices offered by the engines of high-throughput discovery. A lead candidate needs to possess adequate bioactivity, appropriate physical-chemical properties to enable formulation development, the ability to cross crucial membranes, reasonable metabolic stability and appropriate safety and efficacy in humans. Predicting how a drug will behave in humans before clinical testing requires a battery of sophisticated in vitro tests that complement traditional in vivo animal safety assessments. This review discusses how to strategically identify which non-clinical studies should be performed to provide the required guidance and comfort to stakeholders involved in clinical drug testing.
药物研发是一项充满风险的事业。成败往往取决于从高通量发现引擎提供的众多选择中挑选一两种分子进行开发。候选先导化合物需要具备足够的生物活性、合适的物理化学性质以促进制剂开发、穿越关键膜的能力、合理的代谢稳定性以及在人体中适当的安全性和有效性。在临床试验之前预测药物在人体中的行为需要一系列复杂的体外试验，以补充传统的体内动物安全性评估。本综述讨论了如何从战略上确定应开展哪些非临床研究，以便为参与临床药物试验的利益相关者提供所需的指导并使其安心。
