Marked and prolonged serotonin toxicity in a tramadol-poisoned patient with a pharmacokinetic study.

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.

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.

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.

CONCLUSION:

Marked and prolonged serotonin toxicity was attributed to increased M2 production due to paroxetine- and propranolol-related CYP2D6 inhibition of tramadol metabolism.

• Authors: Guillaume Bianconi, Isabelle Malissin, Laurence Labat, Nihel Khoudour, Pascal Houzé, Nicolas Pallet, Bruno Mégarbane, Xavier Declèves
• Journal: Clinical toxicology (Philadelphia, Pa.) (Clin Toxicol (Phila)) Vol. 60 Issue 3 Pg. 382-385 (Mar 2022) ISSN: 1556-9519 [Electronic] England
• PMID: 34287102 (Publication Type: Case Reports, Journal Article)

Chemical References

• Serotonin
• Tramadol
• Cytochrome P-450 CYP2D6

Topics

• Adult
• Cytochrome P-450 CYP2D6 (genetics, metabolism)
• Humans
• Male
• Serotonin (toxicity)
• Tramadol (poisoning)
• Young Adult