Development of a Dosing Regimen for a Liver-Targeted Polymeric Prodrug
Start Date
April 2025
Location
2nd floor - Library
Abstract
Malaria, specifically the species Plasmodium vivax, is extremely widespread. Global warming is projected to increase the number of areas affected by malaria. The only FDA approved therapies (8-aminoquinoline [8-AQ] drugs) conflict with a common enzymopathy, glucose-6-phosphate-dehydrogenase (G6PD) deficiency. If a patient with G6PD deficiency take an 8-AQ drug, it can cause severe anemia, renal failure, and death. Therefore, there is an increased interest in developing a treatment that can applicable to everyone. A previous study by Pottenger et al. (2024) examined the use of liver-targeted polymer prodrugs. When comparing the original drug to the drug with an altered polymer, the addition of the polymer caused a lower concentration of the drug in the plasma, which would improve the original adverse effects. Pottenger et al. (2024) also used liver cells to evaluate IC50, providing the optimal drug concentration. I used their pharmacokinetic data to make a one-compartment model with a pooled fit, first order absorption, and lag time. My model fit the data well so I used it to perform drug simulations. By combining their separate experiments, I found a discrepancy between the IC50 results and achieving a realistic dose. Further studies should be done to find a liver-targeted prodrug with a more favorable profile.
Development of a Dosing Regimen for a Liver-Targeted Polymeric Prodrug
2nd floor - Library
Malaria, specifically the species Plasmodium vivax, is extremely widespread. Global warming is projected to increase the number of areas affected by malaria. The only FDA approved therapies (8-aminoquinoline [8-AQ] drugs) conflict with a common enzymopathy, glucose-6-phosphate-dehydrogenase (G6PD) deficiency. If a patient with G6PD deficiency take an 8-AQ drug, it can cause severe anemia, renal failure, and death. Therefore, there is an increased interest in developing a treatment that can applicable to everyone. A previous study by Pottenger et al. (2024) examined the use of liver-targeted polymer prodrugs. When comparing the original drug to the drug with an altered polymer, the addition of the polymer caused a lower concentration of the drug in the plasma, which would improve the original adverse effects. Pottenger et al. (2024) also used liver cells to evaluate IC50, providing the optimal drug concentration. I used their pharmacokinetic data to make a one-compartment model with a pooled fit, first order absorption, and lag time. My model fit the data well so I used it to perform drug simulations. By combining their separate experiments, I found a discrepancy between the IC50 results and achieving a realistic dose. Further studies should be done to find a liver-targeted prodrug with a more favorable profile.
