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- W39357199 abstract "High-dose pharmacologic ascorbate has promise as an adjuvant to traditional therapies for cancer. It is hypothesized that the peak plasma concentration is a key determinant in treatment efficacy. From the Phase I clinical trails on the use of pharmacological ascorbate as an adjuvant to gemcitabine in the treatment of stage IV pancreatic cancer at the University of Iowa Hospitals and Clinics, we found that monitoring plasma ascorbate concentration [AscH]pl with each infusion is both very time consuming and expensive for large scale implementation. A method to determine the amount and protocol to infuse ascorbate to achieve a desired patient [AscH]pl would be of great benefit. Current models lack flexibility for various infusion protocols. Additionally, constructing a model of ascorbate pharmacokinetics would allow investigation of an optimal dosing regime to maintain a constant plasma ascorbate concentration. A mechanistic model and an empirical model were developed and validated. The mechanistic model suitably replicated the results obtained in the clinical trial but contained too many variables to be useful in a clinical setting. The empirical model showed good results in replicating the trial results and requires only a few easily measured variables to generate clinically relevant predictions. Separately, the the kinetics of glucose-6-phsophate dehydrogenase (G6PD) were simulated. Simulations showed that G6PD exhibits a response capacity, defined as the difference between the activity when all intracellular NADP is oxidized" @default.
- W39357199 created "2016-06-24" @default.
- W39357199 creator A5027130542 @default.
- W39357199 date "2018-11-29" @default.
- W39357199 modified "2023-10-11" @default.
- W39357199 title "Predicting plasma ascorbate levels upon infusion and biochemical implications for glucose-6-phosphate dehydrogenase deficient patients" @default.
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- W39357199 doi "https://doi.org/10.17077/etd.810wwaw7" @default.
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