Shared Resource: PK/PD Core Lab

July 6, 2015
By: William Alexander, Writer, DCI
Ivan Spasojevic, PhD, co-director of PK/PD Core Laboratory, poses with the state-of-the-art LC/MS/MS, AB/Sciex API 5500 QTrap, a sophisticated instrument used for drug discovery and metabolism research.

Romulo S. Sampaio, MS, a visiting PhD student from the University of Paraiba in Brazil, extracts a radio protective agent before LC/MS/MS analysis. The drug candidate will be followed as part of the Phase I study involving glioma patients at Duke. Sampaio is supported by the Brazilian government for a one-year stay to work on metalloporphyrin projects and learn analytical techniques.Please Note: The PK/PD Core Lab is one of two labs making up the Pharmaceutical Research Shared Resource. Click here to read about the Investigational Chemotherapy Service, the other half of the Shared Resource.

Developing a cancer treatment requires understanding two related subjects: pharmacokinetics, or what the body does to a drug, and pharmacodynamics, or what a drug does to the body. These complex reactions and interactions begin the moment a treatment enters the body and continue until it is fully metabolized.

The study of pharmacokinetics (PK) helps researchers to understand and measure factors such as how efficiently the drug gets into the bloodstream, the concentrations it reaches, how quickly it penetrates the target tissue (e.g. tumor), to which extent it is metabolized, and how long it stays in the target and other organs, and the body as a whole. Pharmacodynamics (PD) allows researchers to analyze in detail how a treatment affects the multiple tissues, both at the cellular and at the tissue level. The information obtained is critical for optimal treatment – maximizing the drug effect while staying below the allowed threshold of toxicity.

The PK/PD Core Lab, a part of the Pharmaceutical Research shared resource, provides state-of-the-art equipment, analysis and expertise to help researchers with these and related areas of their projects. Directed by Ivan Spasojevic, PhD, and located within the orange zone of the Duke Clinics building, the PK/PD Lab offers comprehensive PK/PD support which includes design and execution of PK/PD preclinical experiments and Phase I/II clinical studies, analysis of small molecules such as drugs, drug metabolites, physiological metabolites, and biomarkers (HPLC and LC/MS/MS), as well as PK/PD modeling and calculations..

“We take pride in the breadth and depth of the work the PK/PD Core Lab offers,” says Spasojevic. “It is our mission to offer state-of-the-art and timely support to our researchers in both preclinical and clinical stages of drug development. This includes everything from help in experiment design, sample collection and storage, de-novo analytical assay development, measuring minuscule levels of drugs and metabolites in plasma and small tissue samples, designing an optimal dosing regimen for efficacy studies, to helping with data interpretation and publishing.”

The laboratory of David Kirsch, MD, PhD, is one of the teams whose research is possible because of the PK/PD shared resource. The Kirsch lab recently completed a phase I clinical trial of a protease activatable probe, a novel new technique to identify tumor removals. The probe is a solution of molecules delivered intravenously. The molecules travel through the bloodstream and light up when they encounter sarcoma tumors cells, making the tumors easier to find and remove.

With further research, this probe could allow surgeons to be more confident they have fully removed a tumor while reducing the amount of removed surrounding healthy tissue, says Melodi Whitley, a MD/PhD student who is leading work on this project.

“The PK/PD core has been instrumental to our work,” said Whitley. “All of our patients had to have blood drawn at regular intervals to measure how the concentration of the probe was changing and how much was activated. We’ve been in constant contact with Ivan’s team about our goals for the project and how to achieve them.”

The completed trial will allow the Kirsch lab and other researchers to further evaluate the safety of protease activatable probes, as well as their efficacy and possible use for other cancers.

The PK/PD Lab, meanwhile, is constantly working to expand the scope of its services. “Finding drugs and metabolites in tissues such as bone, fat, skin, tumors, or breast milk is more difficult than plasma, but we’re looking hard for new and more accurate ways to do this,” said Spasojevic. “Other labs see a challenge like this and shy away from it. We’re embracing that and other challenges as the top-tier position of our institution requires.”

Visit the Pharmaceutical Research shared resource webpage.