Studies in early clinical development

6. Medicines Interaction (Drug-Drug Interaction, DDI) studies

The objective of medicines interaction studies is to evaluate the effect of concomitant medication on the medicines pharmacokinetics, and the effect of the medicine on the pharmacokinetics of concomitant medications. Similar studies can also be conducted to evaluate interaction with substances other than medicines (recreational drugs, opioid substitution therapies, etc) although these studies may pose difficult procedural challenges.

Medicine interaction studies are guided by in vitro effects and are preferably conducted using a crossover trial design, though sometime a parallel group design if the half-life (t1/2) of the medicine is long. The studies are conducted with healthy volunteers or with patients if it is desirable to evaluate pharmacodynamics endpoints or when the medicines are too toxic (e.g. anticancer medicine).

The choice of dosage, dosing intervals, routes and timing of co-administration, and number of doses should maximise the possibility of detecting an interaction and mimic the clinical setting.

The degree of interaction (inhibition/induction) is typically classified by the change in the absorption of one of the drugs, calculated as the area under the curve (AUC) of the substrate.

The information gained from medicine interaction studies:
  • Labelling instructions accordingly for the Package Leaflet (PL) in the section on ‘taking other medicines’