Impact of nutritional status on the pharmacokinetics of erlotinib in rats

Biopharmaceutics & Drug Disposition
A Pérez-PitarchM Merino-Sanjuán

Abstract

Malnourishment is a complex condition in which physiopathological changes take place in multiple systems as a result of energy, protein and nutrient deficiency. The purpose of this study was to evaluate, using an experimental animal model, the impact of nutritional status on the pharmacokinetic profile of erlotinib, a reversible, highly selective, human epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor. Two groups of rats -WN (well-nourished) and UN (undernourished) - were fed with different diets for 23-26 days. Rats were assigned randomly to one of three erlotinib treatments (n = 42) consisting of a single dose administered intravenously (i.v.), via oral solution or via oral suspension. Blood samples were assayed for erlotinib concentration. A population pharmacokinetic model was developed and pharmacokinetic parameters obtained in UN rats were compared with those in WN rats. Erlotinib clearance suffered a 5% decrease in the mild-undernutrition status. Moreover, when the drug was administered orally as a suspension, the extent and rate of absorption underwent a 20% increase in UN rats. The results of this study might help to explain, at least in part, the variability of erlotinib treatment and could repre...Continue Reading

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Citations

Mar 30, 2017·Nutrition and Cancer·Alejandro Pérez-PitarchMatilde Merino-Sanjuán
Mar 29, 2018·European Journal of Drug Metabolism and Pharmacokinetics·Feng-Ling YuHe Zhu

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