The effect of nutritional status on the pharmacokinetic profile of acetaminophen

Nutritional imbalance (low protein / high fat) is a public health problem affecting many people in developing and developed nations. Such an imbalance will influence pathophysiological homeostasis in individuals and thereby considerably impact drug pharmacokinetics. It was reported that short-term fasting increases acetaminophen exposure in healthy subjects, whereas no effect was observed after a high-fat diet. These findings suggest the necessity of considering nutritional status when assessing the risk of acetaminophen-induced hepatotoxicity. Additionally, the role of nutrition status on the pharmacokinetic profile of acetaminophen (APAP) at toxic doses is either scanty or not available. With this background, we aimed to compare the effects of nutrition status on the pharmacokinetic profile of APAP at a toxic dose in three different dietary regimens like - Normal diet (ND), Low protein diet (LPD), and High-fat diet (HFD). Balb/C female mice were divided into three groups after weaning, and for the next 15 weeks, they were fed with their respective diets (ND, LPD, and HFD). After that, mice were dosed with APAP (300 mg/kg p.o), and blood sampling was done at different time intervals and centrifuged at 3000 rpm for 5 min to collect plasma samples. Plasma samples were analyzed using the HPLC method. Data analysis was done by Non-compartment analysis using Phoenix WinNonlin 8.3 software. LPD group shows higher values of C-max, t(max), t(1/2), and AUC(0-4), AUC(0-x) values than ND and HFD groups. Both Cmax and AUC follow the pattern of drug exposure where LPD > ND > HFD. In conclusion, nutrition in the diet alters APAP pharmacokinetic profile at a toxic dose in three different diet regimes. Further study on CYP450 concentration and activity is essential to understand the pharmacokinetics difference between these dietary regimens.