A research team from the UNC Eshelman School of Pharmacy, UNC School of Medicine, and University of Kentucky College of Pharmacy has received a $75,000 grant to investigate whether elevated renal clearance in patients with traumatic brain injury compromises therapeutic drug concentrations.

Denise Rhoney
Denise Rhoney, PharmD

The award is part of the priority effort by the National Institutes of Health Clinical and Translational Science Award program to promote interinstitutional collaboration and to fund innovative translational research projects to advance patient care.

This is the first award of its kind for the UNC Eshelman School of Pharmacy and an institutional partner outside the state of North Carolina and represents a new collaboration in an important area of research, says Denise Rhoney, PharmD, chair of the School’s Division of Practice Advancement and Clinical Education.

“Each institution brings strengths to this collaboration to more effectively advance research in the area of medication optimization in critically ill patients,” Rhoney says.

Treating Medical Complications in Critically Ill Patients

Critically ill patients suffer high rates of medical complications, many of which may be due to suboptimal prevention or treatment due to the limited understanding of the increased drug clearance that accompanies critical illness, Rhoney says. This condition—known as augmented renal clearance or ARC—is the enhanced elimination of drugs to a magnitude that potentially affects patient outcomes.

“Critically ill patients experiencing ARC have the potential to eliminate drugs more quickly than we currently anticipate, increasing the risk for developing or undertreating medical complications,” says Denise Rhoney, PharmD.

The majority of drugs administered to critically ill patients are dosed using a standard regimen established in non-critically ill patients without therapeutic drug monitoring, she says.

ARC Compromising Renally Eliminated Drug Therapeutic Concentrations

UNC and UK are sites for a small clinical trial of forty critically ill patients with traumatic brain injury. In these patients, serum and urine concentrations of levetiracetam will be collected. Levetiracetam is a renally eliminated antiepileptic drug that is commonly used in patients with traumatic brain injury to prevent seizures.

“We’re choosing TBI as the first patient population that we’re studying drug concentrations in because literature already exists demonstrating patients with TBI experience a high incidence of ARC,” says Kathryn Morbitzer, PharmD, a neurocritical care pharmacotherapy academic fellow at the School.

“Levetiracetam is routinely given for the first seven days after TBI for seizure prophylaxis, so we will be using it as a probe medication to investigate whether ARC compromises renally eliminated drug therapeutic serum concentrations,” Morbitzer says.

As part of this study, the first population pharmacokinetic model in patients with a high prevalence of ARC will also be built.  This will enable the researchers to simulate dosing strategies of levetiracetam in patients with TBI to achieve therapeutic concentrations.

A Promising Collaboration

This study represents a new collaborative research team in an important area of research.  While the collaborative grant bridges a research relationship with the University of Kentucky College of Pharmacy, it also highlights the strength in the Partnership in Patient Care with UNC Hospitals, Rhoney says.

“The information we gain from this study will pave the way for future studies to investigate other renally eliminated drugs and other critically ill patient populations where ARC may occur, along with methods for monitoring renally eliminated drugs in patients with ARC, and the impact on pharmacodynamic properties,” Rhoney says.

The Team

UNC Eshelman School of Pharmacy Division of Practice Advancement and Clinical Education

  • Kathryn Morbitzer, PharmD, is a neurocritical care pharmacotherapy academic fellow and adjunct instructor.
  • Denise Rhoney, PharmD, is the Ron and Nancy McFarlane Distinguished Professor and chair of PACE.
  • Kelly Sullivan, PharmD, is an adjunct assistant professor and a clinical pharmacy specialist in neurocritical care/neurosurgery.
  • Emily Durr, PharmD, is an assistant professor of clinical education and a clinical pharmacy specialist in neurocritical care and neurosurgery.

UNC Eshelman School of Pharmacy Division of Pharmacotherapy and Experimental Therapeutics

  • Heyward Hull, PharmD, MS, is a clinical professor.
  • Julie Dumond, PharmD, MS, is an assistant professor.

UNC School of Medicine

  • Dedrick Jordan, MD, PhD, is an associate professor of neurology and neurosurgery, chief of the Division of Neurocritical Care, and medical director of the Neurosciences Intensive Care Unit
  • Mark Weaver, PhD, is a research assistant professor.

University of Kentucky College of Pharmacy

  • Aaron Cook, PharmD, is an assistant adjunct professor and clinical coordinator of neuroscience-pulmonary/critical care.
  • Jimmi Hatton-Kolpek, PharmD, is a professor of pharmacy and neurosurgery.
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