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The effect of a lipid suspension on amitriptyline disposition

N A Minton1, A G Goode, J A Henry

  • 1Poisons Unit, Guy's Hospital, London, UK.

Archives of Toxicology
|August 1, 1987
PubMed

Insights

Lipid emulsion infusion did not significantly alter plasma levels of amitriptyline and its metabolite, nortriptyline, in healthy volunteers. This suggests lipid resuscitation is unlikely to significantly impact the severity of amitriptyline toxicity.

Area of Science:

  • Clinical Pharmacology
  • Toxicology
  • Emergency Medicine

Background:

  • Amitriptyline is a tricyclic antidepressant with a narrow therapeutic index.
  • Tricyclic antidepressant overdose can lead to severe toxicity, including cardiotoxicity and neurotoxicity.
  • Lipid emulsion has been proposed as a potential antidote for lipophilic drug overdoses.

Purpose of the Study:

  • To investigate the effect of lipid emulsion infusion on plasma concentrations of amitriptyline and its active metabolite, nortriptyline, in healthy volunteers.
  • To assess the potential of lipid emulsion to alter the pharmacokinetics of amitriptyline.

Main Methods:

  • Four healthy volunteers received a 5-hour infusion of either lipid emulsion or saline on separate occasions.
  • Plasma levels of amitriptyline and nortriptyline were measured at the end of each infusion.
  • Pharmacokinetic parameters were analyzed to determine the impact of lipid emulsion.

Main Results:

  • Mean plasma levels of amitriptyline plus nortriptyline were 14% higher at the end of the lipid infusion compared to saline.
  • This observed increase in plasma levels was not statistically significant.
  • No significant alterations in the pharmacokinetic profile of amitriptyline were detected.

Conclusions:

  • Lipid emulsion infusion is unlikely to materially affect the severity of amitriptyline intoxication.
  • Further research may be needed to definitively rule out any minor effects in overdose scenarios.

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