Design of antiretroviral drug interaction studies.
OBJECTIVE
Pharmacokinetic and/or pharmacodynamic drug interactions can occur as a result of treatment with antiretrovirals. Elucidating the mechanism, direction, and magnitude of an interaction, as well as its clinical impact, can be facilitated by proper study design. Two approaches may be considered: assessment based on full pharmacokinetic profiles within a conventional drug interaction trial, or a population pharmacokinetic analysis as a part of a larger trial. Consideration should be given to the population (i.e. healthy volunteer or HIV infected), dosing and administration of medications, and interpretation of findings. Dosing recommendations should be based on the clinical relevance of the interaction.


RESULTS
Guidance documents on the conduct of clinical drug interaction study designs are summarized and applied to the design of antiretroviral drug interaction trials.


CONCLUSIONS
Designing an antiretroviral drug interaction trial poses unique challenges, associated with the conditions and the drug combinations of the intended population. A rational study design can provide insights into antiretroviral pharmacology and allows the clinician to treat more effectively.
Kakuda
Thomas N
TN
Tibotec, Inc., Yardley, Pennsylvania 19067, USA. tkakuda@tibus.jnj.com
Schöller-Gyüre
Monika
M