Marked and prolonged serotonin toxicity in a tramadol-poisoned patient with a pharmacokinetic study.
Clin Toxicol (Phila)
; 60(3): 382-385, 2022 Mar.
Article
in En
| MEDLINE
| ID: mdl-34287102
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tramadol
/
Serotonin
Limits:
Adult
/
Humans
/
Male
Language:
En
Journal:
Clin Toxicol (Phila)
Journal subject:
TOXICOLOGIA
Year:
2022
Document type:
Article
Affiliation country: