Observational studyClinical pharmacokinetics2016
Morbidly Obese Patients Exhibit Increased CYP2E1-Mediated Oxidation of Acetaminophen.
Observational study in Clinical pharmacokinetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 53 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Pharmacokinetics and Safety of Treatment With Paracetamol in Children and Adults With Spinal Muscular Atrophy and Cerebral Palsy
Pharmacokinetics and Pharmacodynamics of Intravenous Paracetamol/Acetaminophen in Morbidly Obese and Non- Obese Patients.
Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 citations in OpenAlex.
- The effect of obesity, macronutrients, fasting and nutritional status on drug-metabolizing cytochrome P450s: a systematic review of current evidence on human studies.European journal of nutrition · 2021Pooled it
- Effects of Fomepizole on Acetaminophen Oxidative Metabolism: A Randomized, Crossover Study in Human Volunteers.Clinical pharmacology and therapeutics · 2026Trial
- The Effect of 4-Methylpyrazole on Oxidative Metabolism of Acetaminophen in Human Volunteers.Journal of medical toxicology : official journal of the American College of Medical Toxicology · 2020Trial
- Higher chlorzoxazone clearance in obese children compared with nonobese peers.British journal of clinical pharmacology · 2018Trial
- Influence of Morbid Obesity on the Pharmacokinetics of Morphine, Morphine-3-Glucuronide, and Morphine-6-Glucuronide.Clinical pharmacokinetics · 2017Trial
- Exposure to acetaminophen and all its metabolites upon 10, 15, and 20 mg/kg intravenous acetaminophen in very-preterm infants.Pediatric research · 2017Trial
- Impact of CYP2E1 Polymorphisms on Preoperative Paracetamol Analgesic Response in Patients with Lower Extremity Fractures.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Semi-Physiological Population Pharmacokinetic Modeling of Oral and Intravenous Paracetamol to Quantify Presystemic Metabolism and Enterohepatic Recirculation.CPT: pharmacometrics & systems pharmacology · 2026Article
- Pharmacokinetics and Childhood Obesity: Pathophysiological Basis and Challenges in Choosing the Ideal Body Size Descriptor.Pharmaceuticals (Basel, Switzerland) · 2025Review
- A Novel Maturation Equation for Hepatic Clearance Across Preterm, Term Neonates, Children, and Adults: Application to Paracetamol and Its Metabolite.Journal of clinical pharmacology · 2025Article
- Recent advances in alcohol metabolism: from the gut to the brain.Physiological reviews · 2025Review
- Examining the Impact of Diet-and-Exercise-Induced Weight Loss on Drug Metabolism and Gastric Emptying in Patients with Obesity.Journal of clinical pharmacology · 2025Article
- The potential of curcumin in mitigating acetaminophen-induced liver damage.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Obesity-related drug-metabolizing enzyme expression alterations in the human liver.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Article
- Amelioration of Acetaminophen-Induced Hepatic Oxidative Stress and Inflammation by RNAi TargetingCurrent issues in molecular biology · 2025Article
- Population Pharmacokinetics of Intravenous Paracetamol and Its Metabolites in Extreme Preterm Neonates in the Context of Patent Ductus Arteriosus Treatment.Clinical pharmacokinetics · 2024Article
- A guide to developing population files for physiologically-based pharmacokinetic modeling in the Simcyp Simulator.CPT: pharmacometrics & systems pharmacology · 2024Article
- Acute pain management in patients with severe obesity.BJA education · 2024Review
- Impact of Obesity on Hepatic Drug Clearance: What are the Influential Variables?The AAPS journal · 2024Article
- When will the Glomerular Filtration Rate in Former Preterm Neonates Catch up with Their Term Peers?Pharmaceutical research · 2024Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionAcetaminophen (paracetamol) is mainly metabolized via glucuronidation and sulphation, while the minor pathway through cytochrome P450 (CYP) 2E1 is held responsible for hepatotoxicity. In obese patients, CYP2E1 activity is reported to be induced, thereby potentially worsening the safety profile of acetaminophen. The aim of this study was to determine the pharmacokinetics of acetaminophen and its metabolites (glucuronide, sulphate, cysteine and mercapturate) in morbidly obese and non-obese patients.
methodsTwenty morbidly obese patients (with a median total body weight [TBW] of 140.1 kg [range 106-193.1 kg] and body mass index [BMI] of 45.1 kg/m(2) [40-55.2 kg/m(2)]) and eight non-obese patients (with a TBW of 69.4 kg [53.4-91.7] and BMI of 21.8 kg/m(2) [19.4-27.4]) received 2 g of intravenous acetaminophen. Fifteen blood samples were collected per patient. Population pharmacokinetic modelling was performed using NONMEM.
resultsIn morbidly obese patients, the median area under the plasma concentration-time curve from 0 to 8 h (AUC0-8h) of acetaminophen was significantly smaller (P = 0.009), while the AUC0-8h ratios of the glucuronide, sulphate and cysteine metabolites to acetaminophen were significantly higher (P = 0.043, 0.004 and 0.010, respectively). In the model, acetaminophen CYP2E1-mediated clearance (cysteine and mercapturate) increased with lean body weight [LBW] (population mean [relative standard error] 0.0185 L/min [15 %], P < 0.01). Moreover, accelerated formation of the cysteine and mercapturate metabolites was found with increasing LBW (P < 0.001). Glucuronidation clearance (0.219 L/min [5 %]) and sulphation clearance (0.0646 L/min [6 %]) also increased with LBW (P < 0.001).
conclusionObesity leads to lower acetaminophen concentrations and earlier and higher peak concentrations of acetaminophen cysteine and mercapturate. While a higher dose may be anticipated to achieve adequate acetaminophen concentrations, the increased CYP2E1-mediated pathway may preclude this dose adjustment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.