Struble Kimberly A, Reynolds Kellie Schoolar
Office of New Drugs, Division of Antiviral Products, US Food and Drug Administration, Silver Spring, Maryland 20993, USA.
Curr Opin HIV AIDS. 2008 May;3(3):325-9. doi: 10.1097/COH.0b013e3282f5f509.
To provide a regulatory perspective on the role of drug interaction information in the development of antiretroviral drugs. Additionally, this review highlights novel studies that provided important information for the safe and effective use of antiretroviral medications. The management of drug interactions in HIV therapy becomes more complex with the introduction of each new drug because many antiretroviral drugs are involved in multiple metabolic and transporter-based interactions. Therefore, a comprehensive preclinical evaluation to characterize a new drug's metabolic pathway(s) followed by in-vivo studies is critical for the safe use of combination antiretroviral therapy.
This review highlights published studies to illustrate several clinical and regulatory issues for in-vivo drug interaction studies such as general design issues, study-population selection, study-design options, use of historical controls and interpretation of results.
Early identification of potential drug interactions can help identify and prioritize clinically important interaction studies essential to the overall development process. Understanding the clinical implications and management of drug interactions can lead to more effective long-term therapy, reduce toxicity, and delay the development of resistance.
从监管角度探讨药物相互作用信息在抗逆转录病毒药物研发中的作用。此外，本综述重点介绍了为抗逆转录病毒药物的安全有效使用提供重要信息的新研究。随着每一种新药的引入，HIV治疗中药物相互作用的管理变得更加复杂，因为许多抗逆转录病毒药物都涉及多种基于代谢和转运体的相互作用。因此，在临床前进行全面评估以确定新药的代谢途径，随后进行体内研究，对于联合抗逆转录病毒疗法的安全使用至关重要。
本综述重点介绍已发表的研究，以阐述体内药物相互作用研究的若干临床和监管问题，如总体设计问题、研究人群选择、研究设计选项、历史对照的使用以及结果解读。
早期识别潜在的药物相互作用有助于识别并优先开展对整个研发过程至关重要的具有临床意义的相互作用研究。了解药物相互作用的临床意义及管理方法可带来更有效的长期治疗，降低毒性，并延缓耐药性的发展。
