RESEARCH REPORT Acetaminophen pharmacokinetics in severely obese adolescents and young adults Mohammed Hakim 1 | Brian J. Anderson 2 | Hina Walia 1 | Dmitry Tumin 1,3 | Marc P. Michalsky 4 | Ahsan Syed 1,5 | Joseph D. Tobias 1,3,5 1 Department of Anesthesiology & Pain Medicine, Nationwide Children's Hospital, Columbus, Ohio 2 Department of Anesthesiology, University of Auckland, Auckland, New Zealand 3 Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio 4 Department of Surgery, Nationwide Children's Hospital, Columbus, Ohio 5 Department of Anesthesiology & Pain Medicine, The Ohio State University College of Medicine, Columbus, Ohio Correspondence Mohammed Hakim, Department of Anesthesiology & Pain Medicine, Nationwide Children's Hospital, Columbus, OH. Email: mohammed.hakim@nationwidechildrens.org Funding information This work was funded from internal funding from the Department of Anesthesiology & Pain Medicine at Nationwide Children's Hospital. Section Editor: Susan Goobie Abstract Background: Intravenous acetaminophen is commonly administered as an adjunctive to opioids during major surgical procedures, but neither the correct pharmacokinetic size descriptor nor the dose is certain in severely obese adolescents undergoing bar- iatric surgery. Methods: Adolescents, 14‐20 years of age, with a body mass index (BMI) ≥95th percentile for age and sex or BMI ≥40 kg·m −2 , presenting for laparoscopic or robotic assisted or vertical sleeve gastrectomy were administered intravenous acetamino- phen (1000 mg) following completion of the surgical procedure. Venous blood was drawn for acetaminophen assay at eight time points, starting 15 minutes after com- pletion of the infusion and up to 12 hours afterward. Time‐concentration data pro- files were analyzed using nonlinear mixed effects models. Parameter estimates were scaled to a 70‐kg person using allometry. Normal fat mass was used to assess the impact of obesity on pharmacokinetic parameters. Results: The study cohort comprised 11 female patients, age 17 SD 2 years with a weight of 125 SD 19 kg and a mean BMI of 46 SD 5 kg·m −2 . The plasma acetami- nophen serum concentration was 17 (SD 4) μg·mL −1 at 10‐20 minutes after comple- tion of the infusion and 5 (SD 6) μg·mL −1 at 80‐100 minutes. A two‐compartment model, used to investigate pharmacokinetics, estimated clearance 10.6 (CV 72%) L·h·70 kg −1 , intercompartment clearance 37.3 (CV 63%) L·h·70 kg −1 , central volume of distribution 20.4 (CV 46%) L·70 kg −1 , and peripheral volume of distribution 16.8 (CV 42%) L·70 kg −1 . Clearance was best described using total body weight. Normal fat mass with a parameter that accounts for fat mass contribution (Ffat) of 0.88 best described volumes. Conclusion: Current recommendations of acetaminophen to a maximum dose of 1000 mg resulted in serum concentrations below detection limits in all patients within 2 hours after administration. Dose is better predicted using total body mass with allometric scaling. KEYWORDS acetaminophen, adolescents, allometry, bariatric surgery, normal fat mass, obesity, pharmacokinetics Received: 19 June 2018 | Revised: 1 October 2018 | Accepted: 10 October 2018 DOI: 10.1111/pan.13525 Pediatric Anesthesia. 2018;1–7. wileyonlinelibrary.com/journal/pan © 2018 John Wiley & Sons Ltd | 1