by Ric Slauter, PhD, DABT
The 20th century saw amazing, life-saving discoveries in medical research. That innovative spirit remains strong in the new century, even as it advances into more complex areas of study, more complicated diseases, and more rigorous standards. Finding a partner who expertly balances those dynamics is key to advancing drug development.
Today’s medical researchers are particularly interested in two inter-related aspects of drug action in the body: pharmacodynamics (PD), which studies the physiologic effects of a drug on the body; and pharmacokinetics (PK), which looks at the time-course of how the body absorbs, metabolizes, and then eliminates the drug. Scientific study of both disciplines is a driving force in drug discovery research because these studies can define the risk and predict the effectiveness of a potential new medicine.
In a previous blog, I cited the four categories in drug metabolism and pharmacokinetics (DMPK) studies where expertise is essential to moving a candidate drug through the pipeline.
- Physiochemical properties, which are the basic “what” and “how” of a compound
- Kinetics of movement through tissues and fluids
- Dynamics of interaction between the drug and the cells, proteins, nucleic acids, other drugs, and various other physiologic elements that influence the ultimate disposition of the drug; and
- Metabolization of the drug, both qualitatively and quantitatively, and how that process impacts the body
Some drugs require a more complicated approach than others and thus it may be more difficult to define the specific properties of the drug that fall within these categories. That is where skilled, experienced scientists are essential to a quality outcome. For example, consider molecules with more complex physiochemical properties, such as low water solubility; determining Ki and IC50 values for CYP interactions and protein binding are especially challenging. Likewise, the difficult process of characterizing the full structure of major drug metabolites—required for a New Drug Application—doesn’t fall within every CRO’s capabilities. Further, the use of radiolabeled compounds to study reactive drug metabolites or the covalent bonds of those metabolites with macromolecules (either in vivo or in vitro) is a specialized skill.
It’s not enough to understand drug metabolism in preclinical species; a strong DMPK partner will effectively determine how those findings translate to humans. This means meeting regulatory demands for preclinical safety data on significant drug metabolites, guidance known as Metabolites in Safety Testing (MIST), while ensuring the exposure to preclinical species is similar to what it would be in a human patient. Without that expertise, additional (and costly) toxicology studies might be necessary.
The recipe for the right DMPK partnership is a competent and experienced science team, sophisticated technology, and expertise across all the right processes. When those elements come together, the oft-quoted words of the late Carl Sagan ring true: “Science delivers the goods.”
Ric Slauter, PhD, DABT, is Senior Director of Drug Metabolism/Pharmacokinetics and Senior Principal Study Director at MPI Research. To learn why MPI Research is the right partner for your DMPK needs, contact us at firstname.lastname@example.org.