A regulatory perspective on the role of drug interactions in antiretroviral drug development.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Office of New Drugs, Division of Antiviral Products, US Food and Drug Administration, Silver Spring, Maryland 20993, USA. kimberly.struble@fda.hhs.gov
Kimberly A
KA
Struble
Kellie Schoolar
KS
Reynolds