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Precision medicine and Malnutrition- A Model based approach to dose chemotherapy in paediatric patients with malnutrition

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This proposed study seeks to investigate the effect of malnutrition on the pharmacokinetics of chemotherapy drugs among pediatric cancer patients in India. By assessing the influence of malnutrition on the serum metabolomic profile, important metabolites that are distinctly lowered or raised in the context of nutritional deprivation will be identified. A population pharmacokinetic model of chemotherapy drugs will be developed including these metabolites as covariates. This approach is expected to allow dose optimization of chemotherapy drugs based on the metabolomic profile of an individual suffering from malnutrition. Such optimization is crucial for mitigating the economic burden associated with chemotherapy-induced adverse events in pediatric oncology. Despite the multifactorial determinants of poor outcomes and reduced tolerability in malnourished pediatric patients undergoing chemotherapy, quantitative analysis of these factors is lacking in current literature. Hitherto no such effort has been used integrating pharmacokinetic, pharmacodynamic, and metabolomic approaches to devise individualized dosing strategies. Therefore, the ultimate goal of this study is to formulate guidelines or algoriths for chemotherapy drugs dosing in pediatric cancer patients, to be disseminated via a mobile/web application. Implementation of these adaptive dosing strategies has the potential to curtail hospitalization costs, minimize late effects, and ultimately enhance outcomes within this vulnerable population.

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