Effects of nutritional status on acetaminophen measurement and exposure

Abstract

Short-term fasting increases acetaminophen exposure in healthy subjects, whereas no effect is observed after a high-fat diet. Furthermore, short-term fasting decreases the accuracy of the enzymatic colorimetric method when measuring relatively low acetaminophen concentrations. This suggests considering nutritional status when assessing the risk of acetaminophen-induced toxicity, although further research at toxic doses is needed.

Impact of malnourishment on the pharmacokinetics of acetaminophen and susceptibility to acetaminophen hepatotoxicity

“…A recent study showed a ~10% decrease in therapeutically dosed acetaminophen clearance in healthy men who had fasted for 36 h 13 . Similarly, a reduction in clearance of roughly 15% was found in men who had fasted for 36 h 14 . Overall, both in animals and humans an apparent effect of malnutrition is increased exposure to total acetaminophen due to a decreased clearance, clinically presented as an increased t½.…”

“…10 In horses, low dosed acetaminophen clearance was reduced by 19% after the horses had been fasted for 72 h. 11 Mehta et al 12 showed a significant decrease in therapeutically dosed acetaminophen clearance in children suffering from protein-calorie malnutrition, resulting in a doubled t½ of 8.14 (±1.30) h compared to 4.33 (±0.52) hours in healthy age-matched controls. A recent study showed a ~10% decrease in therapeutically dosed acetaminophen clearance in healthy men who had fasted for 36 h. 13 Similarly, a reduction in clearance of roughly 15% was found in men who had fasted for 36 h. 14 Overall, both in animals and humans an apparent effect of malnutrition is increased exposure to total acetaminophen due to a decreased clearance, clinically presented as an increased t½.…”

“…In contrast, in the same population, apparent acetaminophen‐glucuronide clearance following a therapeutic dose remained unchanged. 14 Thus, reduced capacity for phase II metabolism due to fasting may lead to a higher fraction of acetaminophen shunted toward phase I (CYP2E1) metabolism, leading to increased formation of NAPQI, irrespective of CYP2E1 activity. 13 , 25 , 31 …”

“…Adding to this, healthy men showed an increase in bilirubin after fasting for 36 h. This may indicate reduced glucuronidation, as bilirubin is a substrate for conjugation with glucuronic acid. In contrast, in the same population, apparent acetaminophen‐glucuronide clearance following a therapeutic dose remained unchanged 14 . Thus, reduced capacity for phase II metabolism due to fasting may lead to a higher fraction of acetaminophen shunted toward phase I (CYP2E1) metabolism, leading to increased formation of NAPQI, irrespective of CYP2E1 activity 13,25,31 …”

An artificial intelligence algorithm for analyzing acetaminophen-associated toxic hepatitis

“…A variety of factors regulate the synthesis of albumin, including nutritional status, cytokines and hormones. 20 In one study, 21 short-term fasting increased acetaminophen exposure in healthy subjects administered oral acetaminophen at 1000 mg. However, in another study including 197 subjects, 6 overweight-obesity status was a significant risk factor for acute liver injury secondary to acute acetaminophen overdose.…”