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Algebraic equation improves drug dosing in liver transplant patients
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Researchers at UCLA may have found a better way to individualize the treatment of patients using a centuries-old branch of mathematics.
The researchers employed an algebraic equation to help them more accurately provide drugs in a small pilot trial of liver transplant patients. The method improved upon physician-guided drug dosing and could be applied to other areas of medicine, the researchers said — including the treatment of infectious diseases. They call it parabolic personalized dosing, or PPD.
“PPD is independent of disease mechanism and is agnostic of indication and could therefore apply beyond transplant medicine to dosing for cancer, infectious diseases, and cardiovascular medicine, where patient response is variable and requires careful adjustments through optimized inputs,” Ali Zarrinpar, MD, PhD, of the division of liver and pancreas transplantation at UCLA’s David Geffen School of Medicine, and colleagues wrote.
Their study, published in Science Translational Medicine, compared the PPD method of drug dosing to the clinical standard of care relying on dosing guidelines or educated guesses. Transplant patients receive immunosuppressant drugs that have narrow therapeutic ranges, Zarrinpar and colleagues wrote — a high dose risks toxicity, while a low dose could spell organ rejection.
“The standard of care is for a provider to adjust the dose of an immunosuppressant drug in response to a whole-blood trough concentration, making an educated guess about factors causing deviation from the target range and the amount by which to adjust the dose in response,” they wrote. “These decisions are made largely on the basis of clinical experience, and patients frequently deviate from the target range, running the alternate risks of toxicity or graft rejection.”
Figure 1. This is an image representing schematic, patient-specific, parabolic response surfaces, which are the keys to personalized medicine.
Source: Dr. Dong-Keun Lee, Dean Ho Group, UCLA
The PPD platform uses clinical data, including drug concentrations in a patient’s bloodstream, to calibrate unique coefficients in an algebraic equation, which helps to pinpoint optimal doses.
In a randomized control trial, Zarrinpar and colleagues compared four liver transplant patients treated with tacrolimus using the PPD method against four liver transplant patients treated according to standard care. The PPD patients stayed within the target drug dosing more frequently than the control group (45.8% vs. 27.4%) and tended to have shorter postoperative hospital stays (mean, 29.5 days vs. 48.8 days).
“Using phenotype to personalize tacrolimus dosing, PPD effectively managed patients by keeping tacrolimus blood trough levels within the target ranges,” Zarrinpar and colleagues wrote. “In a retrospective analysis of the control patients, PPD-optimized prednisone and tacrolimus dosing improved tacrolimus trough-level management and minimized the need to recalibrate dosing after regimen changes.” – by Gerard Gallagher
Disclosure: Zarrinpar reports being a co-inventor on a patent related to this work. Please see the full study for a list of all other authors’ relevant financial disclosures.
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