Document Detail

Nefazodone poisoning: toxicokinetics and toxicodynamics using continuous data collection.
MedLine Citation:
PMID:  12733855     Owner:  NLM     Status:  MEDLINE    
Nefazodone overdose has been reported infrequently. The commonest effects reported are drowsiness, nausea, dizziness, and vomiting, less commonly hypotension and bradycardia. We report a case of single-agent nefazodone poisoning. Serial drug concentrations were taken for quantification of parent drug and metabolites. Clinical findings were documented every 1 to 2 hours. We modeled both the toxicokinetics of nefazodone and correlated this with clinical effects and electrocardiograph (ECG) abnormalities. A 16-year-old female took 2.4 g of nefazodone. She had significant drowsiness in the first 6 hours, associated with hypotension (systolic BP < 90 mmHg; lowest BP 70/30 mmHg) for 18 hours, and mild bradycardia (slowest rate of 56 bpm). She had a prolonged QT/QTc which normalized over 24 hours. She was given charcoal and intravenous fluids and was observed carefully, recovering with no problems. The terminal elimination half-life for nefazodone was 8.3 hours, and its metabolite hydroxy(OH)-nefazodone was 14.6 hours. BP-time curves demonstrated an 18-hour period of hypotension. There was a significant correlation between systolic BPand OH-nefazodone (R2 = 0.602). HR remained between 56 and 66 bpm for 30 hours despite hypotension. QT was significantly correlated with nefazodone (R2 = 0.911) and OH-nefazodone (R2 = 0.797), but no significant relationship between QTc and drug concentrations. The case demonstrates that nefazodone may potentially cause cardiac toxicity, which appears to be concentration-dependent. Although QT was concentration-dependent, this would need confirmation with other cases. Bradycardia, hypotension, and drowsiness are the most significant effects and are maximal in the first 12 hours when parent and metabolite concentrations are high.
Geoffrey K Isbister; L Peter Hackett
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Publication Detail:
Type:  Case Reports; Journal Article    
Journal Detail:
Title:  Journal of toxicology. Clinical toxicology     Volume:  41     ISSN:  0731-3810     ISO Abbreviation:  J. Toxicol. Clin. Toxicol.     Publication Date:  2003  
Date Detail:
Created Date:  2003-05-07     Completed Date:  2003-05-20     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  8213460     Medline TA:  J Toxicol Clin Toxicol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  167-73     Citation Subset:  AIM; IM    
University of Newcastle, Newcastle, Australia.
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MeSH Terms
Antidepressive Agents, Second-Generation / pharmacokinetics*,  poisoning*
Antidotes / therapeutic use
Blood Pressure / drug effects
Charcoal / therapeutic use
Depressive Disorder / drug therapy,  psychology
Electrocardiography / drug effects
Fluid Therapy
Long QT Syndrome / chemically induced,  physiopathology
Triazoles / pharmacokinetics*,  poisoning*
Reg. No./Substance:
0/Antidepressive Agents, Second-Generation; 0/Antidotes; 0/Triazoles; 16291-96-6/Charcoal; 83366-66-9/nefazodone

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