@article{ref1,
title="Marked and prolonged serotonin toxicity in a tramadol-poisoned patient with a pharmacokinetic study",
journal="Clinical toxicology (Philadelphia, Pa.)",
year="2021",
author="Bianconi, Guillaume and Malissin, Isabelle and Labat, Laurence and Khoudour, Nihel and Houzé, Pascal and Pallet, Nicolas and Megarbane, Bruno and Declèves, Xavier",
volume="ePub",
number="ePub",
pages="ePub-ePub",
abstract="BACKGROUND: Tramadol poisoning rarely causes serotonin toxicity, which mechanisms remain poorly understood. We investigated alterations in tramadol pharmacokinetics in a tramadol-poisoned patient who presented with marked and prolonged serotonin toxicity. CASE REPORT: A 21-year-old male self-ingested 750 mg-tramadol, 200 mg-sotalol, 400 mg-propranolol and 6 mg-lorazepam. He was a kidney transplant patient treated with mycophenolate, tacrolimus, prednisone, and paroxetine. He developed transitory cardiovascular failure and prolonged serotonin toxicity requiring sedation, muscle paralysis, and cyproheptadine, with a favorable outcome. <br><br>METHODS: We measured plasma concentrations of tramadol, M1, M2, and M5 using liquid-chromatography-tandem mass spectrometry, calculated elimination half-lives and metabolic ratios of the compounds, and genotyped cytochromes involved in tramadol metabolism. <br><br>RESULTS: Elimination half-lives of tramadol (6.1 h) and M1 (7.1 h) were normal while those of M2 (26.5 h) and M5 (16.7 h) prolonged. M1 metabolic ratio (0.12) was 2-fold reduced, M2 metabolic ratio (197) 1000-fold increased and M5 metabolic ratio (0.12) normal. This metabolic profile in a patient with normal CYP2D6-metabolizer status based on genotyping supports CYP2D6 inhibition by paroxetine and propranolol, two strong mechanism-based inhibitors. Only M2 present in sufficient concentrations up to 48 h could explain the prolonged serotonin toxicity. <br><br>CONCLUSION: Marked and prolonged serotonin toxicity was attributed to increased M2 production due to paroxetine- and propranolol-related CYP2D6 inhibition of tramadol metabolism.<p /> <p>Language: en</p>",
language="en",
issn="1556-3650",
doi="10.1080/15563650.2021.1955912",
url="http://dx.doi.org/10.1080/15563650.2021.1955912"
}