Fascinated by the complexity of drug regimens and the value they have for long-term success of organ transplantation, Rita Alloway, PharmD, FCCP, uses her pharmacology background in the transplantation field. “I still consider transplantation a modern-day miracle that is life-altering when it is successful,” says Dr. Alloway. Examining how to prevent rejection on an individual basis through careful analysis of medications that prevent the immune system from attacking the transplanted organ, Dr. Alloway proves to be a PowerPlayer in the field — she applies her Power2Save in furthering the long-term goal of success for transplant recipients.
Pharmacology in Transplantation
Her concentration narrows in on the smaller percentage of patients who have experienced a period or periods of rejection, rather than the large population of patients who experienced successful transplants. “Current results of multicenter clinical trials typically yield 15 out of 100 patients who experience a rejection episode,” says Dr. Alloway, who has a Doctor of Pharmacy degree from the University of Tennessee, College of Pharmacy. “The question remains, ‘How do we prevent those 15 patients from rejecting the transplanted organ?’” She also examines how to minimize the toxicity — or the degree the medications can damage or cause side effects to the organ — of the entire group.
The interest in this concentration was sparked by an experience early in her career. One of her patients experienced ongoing rejection because of low levels of the immunosuppressant medications — she suspected the patient was not as diligent in taking the medications as they should have been. “However, from emerging new data and the patient’s family medical history, I concluded the patient’s family had a gene that caused her to metabolize or eliminate one of the most potent immunosuppressant drugs very quickly, putting her at risk for rejection despite the fact she was taking her medications correctly,” says Dr. Alloway. Optimizing the patient’s immunosuppressant medications allowed her to prevent another episode where the immune system attacked the transplanted organ.
As a research professor in the College of Medicine at the University of Cincinnati and director of Transplant Clinical research, Dr. Alloway has explored the optimum target level of medications in the blood stream for each individual patient that will result in preventing rejection without developing adverse side effects or toxicity — which is referred to as the study of pharmacokinetics. The challenges, according to Dr. Alloway, are that everyone’s immune system’s are different and they don’t respond exactly the same to immunosuppressive drugs. “The variability in the immune response and the metabolic pathways which eliminate the medication make it difficult to find the optimal regimen for each individual patient,” says Dr. Alloway. “That is only half the battle; then the challenge is to impact the behavior [of a recipient] in a way that will result in adherence [and the person taking the medications as directed].”
More recently, Dr. Alloway is studying target levels of various generic drugs in transplantation. Of particular focus is the immunosuppressant medication tacrolimus (a narrow therapeutic index drug), where the dose to achieve efficacy (ie., prevent rejection) is very close to the dose which results in unwanted side effects. “Ongoing concern exists, not only in medical community, but in the general public, that generic medications may not provide similar quality as brand-name medications,” says Dr. Alloway. “This is of particular concern when important, life-saving medications (like tacrolimus) become available as generic medications. It is important we understand the impact on transplant recipients.”
In the future, Alloway hopes to better monitor patients’ immune responses, provide medications that have fewer side effects, and devise regimens that better fit into a patient’s long-term lifestyle. “As successful as we have been in the short term, there are many areas we can still improve,” says Dr. Alloway. “We are still in the beginning of optimizing transplantation as the gold-standard treatment for end-organ failure.”