Case report of ivabradine intoxication.
Ivabradine is a drug used for the treatment of angina and chronic heart failure in cases of intolerance or insufficiency of response to beta-blocker treatment. A 47-year-old man was admitted to the emergency department of the hospital for a voluntary intoxication with 280 mg of ivabradine: he presented drowsiness and a mild sinusal bradycardia (50 bpm) associated with a well-tolerated low blood pressure at 100/50 mmHg. No complication was noted and he was discharged from the hospital on Day 3. A method for ivabradine assay in serum was obtained using liquid chromatography coupled with a mass spectrometry detection method. After a deproteinization step using QuECHERS salts and acetonitrile, a chromatographic separation was performed using a 5-µm 50 × 2.1 mm Xterra® column (Waters, France). Detection was performed using an LTQ linear ion-trap mass spectrometer equipped with an electrospray ionization source used in a positive ionization mode (ThermoFisher Scientific, San Jose CA, USA) and a detection in full MS(2) scan. The limit of quantification of ivabradine was 10 µg/L, and the method was linear up to 1000 µg/L. The ivabradine concentration in the patient's serum was 375 µg/L. This concentration value was >30 times those measured after therapeutic doses intakes. Nevertheless, the bradycardia was no more severe than the one observed with therapeutic dosage. In conclusion, this case tends to show an absence of correlation between blood concentration and severity of the troubles in cases of overdosage.
1Biological and Forensic Toxicology Unit, Pharmacology and Toxicology Department, University Hospital of Limoges, 2 Avenue Martin-Luther King, 87024 Limoges cedex, France.
François
F
Mathiaux
Sylvain
S
Dulaurent
Frédéric
F
Julia
Jean-Michel
JM
Gaulier
D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000097:blood* / Q000633:toxicity*; D001552:Benzazepines / Q000008:administration & dosage / Q000097:blood* / Q000633:toxicity*; D001919:Bradycardia / Q000097:blood / Q000139:chemically induced*; D062787:Drug Overdose; D006801:Humans; D007022:Hypotension / Q000097:blood / Q000139:chemically induced*; D000077550:Ivabradine; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D021241:Spectrometry, Mass, Electrospray Ionization
D000889:Anti-Arrhythmia Agents; D001552:Benzazepines; D000077550:Ivabradine