药物非临床毒代动力学研究进展

Progress in nonclinical toxicokinetics in drugs

药物非临床毒代动力学是药代动力学在全身暴露评价中的延伸,或为非临床毒性研究的一部分,或为某一专设支持性研究,可为药物临床试验或应用提供安全性依据。目前毒代动力学已由最初的解释毒性试验结果逐渐扩展至毒性机制研究,成为在药物非临床和临床研究间的桥梁,同时其研究范围也扩展至药物代谢产物等的安全性评价中。本文就毒代动力学的实施、复合因素以及国内外研究进展进行综述,并展望其发展新方向。

Toxicokinetics is normally performed as an integral component in nonclinical toxicity studies or as a part in specially designed supportive studies, and it can generate kinetic data at different dose levels for assessment of systemic exposure and providing scientific support evidences for clinical safety issues. Toxicokinetic study has been gradually extended from only explaining toxicity test results to investigate toxic mechanism. It acts as a bridge between nonclinical and clinical studies regarding the drug safety, and becomes more crucial than ever before. Its scope has been further expanded to safety evaluation of drug related substances, such as drug metabolites. This pa- per reviewed the test procedures and complicating factors of toxicokinetic study, and its roles in new drug develop- ment, and a prospect of the further development is also summarized.