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Investigating the molecular basis of altered pharmacokinetics of anticancer drugs under conditions of malnutrition


Nutritional status is one of the factors that cause inter-patient variability in response to anti-cancer drugs. Several studies have shown the effect of malnutrition on toxicity and pharmacokinetics of drugs. These observations are of interest in India due to our large malnourished population. To improve the efficacy of anticancer drugs in malnourished patients, we need to understand the mechanism behind the change in pharmacokinetics and toxicity. We hypothesize that in malnutrition, expression of drug transporters and metabolizing enzymes present in liver, that are responsible for clearance of drugs is changed, causing the increased half-life of these drugs in the body. This also leads to increased exposure of drugs to organs. Additionally, the already stressed organs are more susceptible to toxicity when exposed to anticancer drugs. We are using a diet-based protein deficiency animal model to study these mechanisms through western blotting and RT-PCR techniques.

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