Faculty expert on pharmacokinetics, pharmacodynamics explains importance of field’s specialties

BUFFALO, N.Y. — When you pop a prescription pill into your mouth, you trust it to address the issue it was meant to fix. But what really happens? How is your body processing the drugs and what happens if the dosage or timing is off?

This is where the dual pharmacy specialties — pharmacokinetics (PK) and pharmacodynamics (PD) — ­­­­come into play.

Pharmacokinetics studies how a drug is absorbed into the body over time — how it gets distributed through the blood and to various tissues, how it is metabolized and how quickly or slowly it is eventually eliminated from the body.

Pharmacodynamics looks at how a drug concentration affects various physiological systems in the body, especially interacting with drug targets to produce the ultimate drug responses.

These types of drug studies are significant because half of all adults and 85% of adults 60 and older report taking at least one prescription drug per month. Older adults take four to five drugs monthly, on average.

The University at Buffalo School of Pharmacy and Pharmaceutical Sciences has its own resident expert in the fields of pharmacokinetics and pharmacodynamics: William Jusko, PhD, SUNY Distinguished Professor of Pharmaceutical Sciences.

A faculty member in the pharmacy school since 1972, Jusko served as editor-in-chief of the Journal of Pharmacokinetics and Pharmacodynamics and has worked as a consultant for the Food and Drug Administration’s (FDA) Clinical Pharmacology Advisory Committee; the National Institutes of Health Pharmacology Study Section; the Council for International Exchange of Scholars and many pharmaceutical companies.

Jusko provides a clear understanding of pharmacokinetics and pharmacodynamics as UB, with both a division and a center dedicated to them, is world renowned for its study of these specialties and its training of young scientists.

Why are these dual specialties important?

They’re important because they provide an understanding and determine a drug’s optimum efficacy and help to minimize toxicity. As people are living longer with many comorbidities, there is increasing need to utilize pharmacokinetics and pharmacodynamics to personalize the drug and regimen to match a patient’s needs.

For optimum control of patient therapy, we need to know the correct dosage of a drug, how often it should be taken, and what happens when it’s given to a particular patient with specific physiology, genetics, diseases and other drugs they may be taking. The FDA requires the study of PK and PD in great detail in order to make decisions on whether drugs are safe and effective.

A limited number of scientists are pursuing this field. They go to work in academia, at the FDA and at pharmaceutical companies. There are lots of opportunities for our graduates.

How did you become interested in these dual specialties?

I worked in a drug store in high school where I became interested in pharmacy, and then I came to UB. During pharmacy school, I was invited to work in the laboratory of Gerhard Levy (pharmacy faculty member from 1958-2000 who died in 2017). He helped develop the fields of pharmacokinetics and pharmacodynamics and began the Department of Pharmaceutics in the pharmacy school in 1964.

Working with him sparked my interest in pursuing research at the doctoral level focusing on PK/PD. It has created a very satisfying career for me. I have conducted studies in patients with a variety of diseases and many types of drugs, particularly antibiotics, anti-cancer, anti-diabetic and steroid drugs.

What is an example of how PK and PD can used?

In a recent study that will soon be published in the Journal of Clinical Pharmacology, my student and I reviewed the properties of the six major insulin products given to diabetic patients and what has been measured in terms of time course of insulin and glucose concentrations in the blood.

All insulins were found to increase muscle, fat and other tissue intake uptake of glucose that is utilized for energy production in very similar ways. But the six products differ in their pharmacokinetics from showing rapid to very slow changes. We provided a better understanding of how one can control insulin and glucose concentrations in blood and provided a unified approach for all types of insulin that can help design more personalized dosing regimens.

These measurements are needed when a new insulin product is developed. Companies are now developing new forms of insulin, which may mimic regular insulin in action but still require testing and FDA approval. The hope is that such biosimilar insulins will reduce prices and make insulin products available to more people.

Can you talk about PK/PD from your laboratory experience?

Most of my own laboratory research has dealt with corticosteroids, with the drugs mainly known as prednisone, methylprednisolone and dexamethasone.

The reason many patients were dying from COVID-19 was that they developed cytokine release syndrome (CRS), which means that they had extreme inflammation that affected their lungs in particular. Dexamethasone and methylprednisolone were the best treatments.

We developed a model in rats that mimics what happens during COVID and sought to better understand how dexamethasone, in particular, works. Our animal model was very successful. With our own data, plus information from the literature, we provided a mathematical model of how dexamethasone suppresses inflammation and the time course of its action. From there, we identified a problem — the regimens last used in COVID were not always sufficient.

Many patients should have been getting more drug than the standard dose of 6 milligrams daily for 10 days. We showed that 12 milligrams per day should be given to a great many patients for the 10 days. We have similar ongoing studies with methylprednisolone.

What is the mission of UB’s Center of Excellence for Pharmacokinetics and Pharmacodynamics?

The center provides a way to identify a core group of our faculty who specialize in PK, PD and systems pharmacology. It fosters collaborations, supports trainees and seeks to garner support from pharmaceutical companies and the National Institutes of Health to pursue research in this area.

Since 1993, we’ve offered three-day annual postgraduate courses in PK/PD modeling that we teach to scientists from all over the world. My colleague Don Mager and I have presented the course many times in the Netherlands, Paris, China, Poland and at many U.S. pharmaceutical companies. I gave the course by Zoom in September to 70 scientists at the FDA. We consider ourselves evangelists for PK/PD.

Every May, we offer the same three-day course in Niagara Falls for pharmaceutical scientists from around the globe. We tell people that they come to our area to see two wonders of the world: Niagara Falls and our PK/PD course.

How can pharmacy students apply these specialties to their careers?

Clinical pharmacists today are often entirely responsible for the correct dosing of many drugs in patients, some of whom have complicated comorbidities and are treated with multiple drugs. So, the pharmacists need to know something about PK and PD properties.

Every drug has a product label that anyone can find online. Pharmacists have to be able to understand the information in each product label and answer questions from patients, such as, “Should I take my blood pressure pills in the morning or evening?”

The pharmacist helps translate a lot of scientific and clinical information. The more pharmacists understand about how drugs are handled by the body (PK) and how they control their effects (PD), the better they can help patients manage their diseases and disorders in the safest possible manner.