Drug-Drug Interactions (DDI) analysis

Drug-Drug Interactions refer to the effects that occur when two or more drugs interact with each other, altering their pharmacokinetic or pharmacodynamic properties. These interactions can lead to unexpected side effects, reduced efficacy, or even toxicity in patients.

Understanding and mitigating DDI are paramount to the success of clinical trials and the safety of pharmaceutical products. Through advanced computational modeling and simulation techniques, PhInc provides comprehensive analysis of DDI profiles, helping pharmaceutical companies make informed decisions during clinical stages. By leveraging our expertise in pharmacokinetic modeling, we assist in predicting and evaluating the impact of DDI, thus optimizing trial designs and minimizing risks to patients. Drug-Drug Interactions represent a complex yet manageable challenge in clinical research.

At PhinC Development, we specialize in providing comprehensive solutions for informing, reducing, and eliminating DDI risks in clinical studies. By leveraging our expertise in pharmacokinetic modeling and simulation, we allow to biotechnology companies to go through the step of DDI with confidence, ultimately advancing the development of safer and more effective therapeutics for patients worldwide.

Types of Drug Interactions

Any factor that affects a drug’s pharmacokinetics (PK) or pharmacodynamics (PD) can lead to a drug interaction. While most drug interactions are related to changes in PK due to internal or external influences, some also impact PD. Common types of drug interactions include:

• Médicament – Médicament en vente libre (OTC) : Drug–Over-the-Counter (OTC): Similar to traditional drug–drug interactions (DDIs), OTC medications can alter a drug’s PK or PD, potentially enhancing or diminishing its effects.
• Drug–Food: Food in the gastrointestinal tract can influence drug absorption—either speeding it up, slowing it down, or altering the total amount absorbed—leading to changes in drug concentration and effect.
• Drug–Alcohol: Alcohol commonly interacts with drugs affecting the central nervous system (CNS), often intensifying sedative effects and increasing the risk of CNS depression.
• Drug–Disease: Underlying health conditions can produce physiological changes that significantly alter a drug’s PK or PD, potentially reducing efficacy or increasing toxicity. Certaines pathologies peuvent provoquer des changements physiologiques importants qui altèrent la PK ou la PD d’un médicament, réduisant ainsi son efficacité ou augmentant sa toxicité.
• Drug–Laboratory Test: Certain drugs can interfere with diagnostic lab tests, leading to inaccurate results such as false positives or false negatives.

General Considerations for Designing Clinical DDI Studies

General Considerations for Designing Clinical DDI Studies In the context of pharmacokinetic drug–drug interactions (DDIs), the choice of study design is primarily driven by the study’s hypotheses and objectives. DDI risk assessment is a continuous process throughout drug development, as illustrated in Figure 1. In the early stages, this assessment relies heavily on in vitro, animal, and in silico data. However, as development progresses, the evaluation becomes increasingly informed by emerging clinical data. in vitro, animales et in silico, mais elle est rapidement renforcée par les données cliniques qui s’accumulent au fil du temps.

When a drug is already in advanced development or approved and marketed, new DDI studies may be initiated based on retrospective evaluations of real-world data, spontaneous case reports, or new preclinical findings. The drug may be assessed either as a substrate (i.e., a "victim" of interactions) or as a perpetrator (inhibitor or inducer) of drug-metabolizing enzymes or transporters.

For instance, a 2012 retrospective epidemiologic study highlighted an increased risk of rhabdomyolysis in patients taking both cerivastatin and clopidogrel. This finding prompted further investigation, which confirmed clopidogrel as an inhibitor of the CYP2C8 enzyme.

Refer to Figure 1 for a schematic overview of the clinical DDI evaluation process, including signal detection, risk assessment, study design, interpretation, and possible regulatory outcomes.

Figure 1: Clinical Studies on Drug–Drug Interactions Involving Metabolism and Transport: Methodology, Pitfalls, and Interpretation

Source : Clin Pharma and Therapeutics, Volume: 105, Issue: 6, Pages: 1345-1361, First published: 27 March 2019, DOI: (10.1002/cpt.1435)