Pharmacokinetics of Acetaminophen in patients with obesity compared to non-obese and overweight patients: a prospective observational cohort study
Pharmacokinetics, Obesity, Acetaminophen
Published online: Feb 11 2025
Abstract
Background: Drug dosing in obese patients can be challenging due to changes in pharmacokinetics. It is unclear which body mass descriptors can be used to describe paracetamol pharmacokinetics in obese patients.
Objectives: we sought to identify which body mass descriptor correlated best to specific pharmacokinetic parameters regarding paracetamol: the volume of distribution (Vd) and drug clearance (Cl). Secondly we aimed to identify the differences in pharmacokinetic parameters in obese and non- obese patients.
Design: we conducted a prospective observational cohort study at Ghent University Hospital.
Methods: 25 obese patients (BMI> 35kg/m²) and 7 non-obese patients (BMI< 30 kg/m²), all undergoing laparoscopic abdominal surgery, received a two-gram loading dose of paracetamol. Blood sampling was performed at set intervals. Pharmacokinetic analysis was performed using PKSolver. Descriptive statistics were performed on both patient groups. Correlation coefficients and simple linear regression were calculated for different body mass descriptors and pharmacokinetic parameters
Results: Non obese patients exhibited significantly higher maximum plasma concentrations of paracetamol. Obese patients exhibited significantly higher Vd and Cl. The order of correlation to Vd in our study was LBM>TBW>IBW. Correlation between drug clearance and TBW was significant. There was a weak positive correlation between LBM and drug clearance, which was not statistically significant. There was a near absent correlation between IBW and drug clearance.
Conclusions: When statistically significant, correlations and predictive values between weight descriptors and pharmacokinetic parameters observed in our study were in general weak to very weak. We might conclude that LBM can be used to calculate loading dose of paracetamol and TBW might be suited for calculation of maintenance doses of paracetamol. . Larger randomised controlled trials with less confounders (e.g. liver surgery) and with assessment of toxic metabolites and hepatotoxicity are needed to improve the clinical relevance of our findings.
