by Ric Slauter, PhD, DABT
The strongest rope is one made of multiple cords woven tightly together. Likewise, applying the closely associated tools of pharmacokinetics and pharmacodynamics early in drug development can lift the best candidates above the also-rans.
While pharmacokinetics (PK) and pharmacodynamics (PD) have a strong relationship, they’ve been approached separately in the past: PK at the preclinical discovery phase, helping narrow the number of molecules being evaluated; and PD as an interesting aside for describing the physiological response to a compound. Nowadays, we can create a mathematical model that describes the time it takes for a compound to appear and then vanish from an organism and how that timeline correlates with the body’s responses (PD).
The power of this approach, especially when applied early in a compound’s developmental life, is in its ability to assist in the rank-ordering of molecules for further study based upon their PK-PD characteristics. This is particularly important in small-molecule drug discovery, where thousands of molecules may need to be evaluated.
By applying early PK-PD modeling, researchers look for the most desirable PK properties, the most desirable PD properties in relation to PK findings, and the best pharmacology—that is, the compound that hits the molecular target most effectively.
From an efficiency perspective, our team at MPI Research is building an increasingly sophisticated understanding of PK-PD relationships and using that knowledge to predict which molecules will work in a given area of study. That can cut the number of molecules to evaluate in the first place, meaning faster selection and more rapid development.
Of course, early PK-PD modeling isn’t a silver bullet. Drug research will continue to use many pharmacological and toxicological tests. But applied effectively, a thorough understanding of the PK-PD relationship will narrow the playing field and enhance our understanding of what to expect as a drug candidate moves through the pipeline.
The opportunities go well beyond small molecules to encompass biologicals and other therapeutics and disease indications. For example, we might be studying a certain molecule for its potential to affect Alzheimer’s plaques, but we notice that dosing an organism causes a drop in blood pressure. That’s where a look at the pharmacodynamics of its cardiovascular effects will help us better understand the compound and how (or whether) to move it forward.
Further, we can use the PK-PD relationship to select the most appropriate species for predicting human outcomes prior to FDA-required safety and efficacy testing. This can avoid costly and time-consuming follow up studies when a poor model is chosen.
Early understanding of the PK-PD relationship is a vital tool in selecting better compounds for study and generating deeper knowledge of those that are chosen. We’re wielding this tool at MPI Research to help our Sponsors cut time and cost while potentially reducing failures at the clinical stage.
Ric Slauter, PhD, DABT, is Senior Director of Drug Metabolism/Pharmacokinetics and Senior Principal Study Director at MPI Research. To find out how early PK-PD modeling can enhance your development needs, contact us at email@example.com.