DMPK studies, which include absorption, distribution, metabolism, excretion (ADME) and pharmacokinetic (PK) studies, allow drug developers to evaluate the intrinsic PK properties of a drug or biologic for establishing safe and effective clinical dosage regimens. DMPK studies also help to evaluate the potential for interactions between medications whereby co-administration in the patient population results in changes in the PK of one (or both) therapeutics.
Clinical DDIs often occur through changes in the expression or function of metabolic enzymes or transporters, resulting in changes in drug clearance and the potential formation of active or toxic metabolites. Clinical DDIs can also occur with certain foods (e.g., grapefruit juice) or supplements. Given that such changes cause adverse effects or loss of efficacy, the propensity for clinical DDIs is an important consideration in candidate selection, dose selection, and in defining an appropriate clinical development strategy.
Guidance documents from regulatory agencies (FDA guidance, EMA guidance, PMDA guidance) outline the importance of DMPK studies in predicting a drug’s potential as either a perpetrator or victim of DDIs. Well-designed in vitro studies that investigate a drug’s interactions with drug metabolizing enzymes and drug transporters can help identify risks before first-in-human (FIH) trials, plan clinical DDI studies more efficiently, or anticipate labeling restrictions if necessary. DMPK studies also allow Discovery scientists to achieve reasonable structural modifications so that the drug’s PK can potentially be improved. A comprehensive DMPK strategy that adequately considers DDIs during drug discovery and development is of the utmost importance.
Allucent has experience designing and analyzing DDI studies at all phases of drug development. We build upon the learnings gained during nonclinical development to define fit-for-purpose clinical DDI strategies based on your program’s specific needs and regulatory guidance recommendations. Additionally, we use model-informed drug development (MIDD) approaches such as physiologically-based PK (PBPK) modeling to leverage the results of nonclinical DDI studies in combination with clinical PK data. Using these techniques to perform “virtual” clinical DDI studies often enables a more streamlined and efficient clinical DDI strategy, requiring fewer studies or even avoiding clinical DDI studies altogether.
Drug-Drug Interaction (DDI) Strategy Services:
- Design and interpret in vitro DDI studies
- Design and analyze clinical DDI studies
- PBPK modeling and simulation of clinical DDIs