DDI trials are special PK trials. Background: Drug-drug interactions can occur at any of the following levels: absorption, distribution, binding at the receptor, metabolization, or elimination. Clinically relevant interactions may occur as a result of induction or inhibition of an enzyme system by a certain drug, while another substrate is being metabolized via that enzyme system.
A relevant interaction can occur when a substrate is predominantly decomposed by a certain enzyme system, and that enzyme system is induced or inhibited by another drug. An important class of enzymes that are prone to interactions are monooxygenases of the cytochrome P450 family. Investigational compounds which are predominantly metabolized by one of these enzymes should be investigated in a dedicated DDI study together with a known test substance which is known to inhibit or induce that enzyme system. The same applies if the investigational compound itself is an inhibitor or inductor of a certain cytochrome isoenzyme. Whether the DDI study is to be designed as a single-dose or multiple-dose study depends on different factors: i) intended acute or chronic use of the substrate or interacting drug substance, ii) safety considerations in case of narrow therapeutic range, iii) pharmacokinetic or pharmacodynamic properties, iv) whether an inhibition or induction is under investigation.
Inamed’s clinical pharmacology experts would be pleased to provide you with further advice in this regard and identify the most appropriate study design that is tailored to your investigational compound taking into account all scientific and regulatory aspects.