title: An assessment of the in vivo effects of intravenous lipid emulsion on blood drug concentration and haemodynamics following oro-gastric amitriptyline overdose.
abstract: BACKGROUND
  Overdose with lipophilic drugs, such as amitriptyline, may cause cardiotoxicity in overdose. Severe poisoning can be resistant to traditional treatments. Intravenous lipid emulsion (ILE) has been recommended as a novel therapy for the treatment of such overdoses; however, a little is known about the effects of ILE-infusion on drug concentration and haemodynamics in the early/absorptive phase after oral poisoning.
  
  
  METHODS
  Thirty minutes after oro-gastric administration of amitriptyline (70 mg/kg), either 20% intravenous lipid emulsion (ILE), 8.4% sodium bicarbonate or Hartmann's solution was infused to anaesthetized and ventilated rodents (n = 10 per group). Heart rate, blood pressure, cutaneous ECG - QRS interval duration (QRS-d), and survival were serially recorded over 120 min. Blood drug concentrations were also collected during this period. Continuous variables were compared using one-way ANOVA.
  
  
  RESULTS
  ILE infusion significantly decreased the survival compared to other treatments (10% ILE vs 70% bicarbonate vs 70% Hartmann's solution, p = 0.005). There was a gradual prolongation of QRS-d and fall in blood pressure over time compared to baseline (T0) measurement for both ILE and Hartmann's solution treatments. This was associated with significantly increased blood AMI concentration with ILE treatment at T60, T90 and T120 min to the other treatments (p < 0.02).
  
  
  CONCLUSIONS
  Administration of ILE early after oral amitriptyline overdose resulted in worse survival and no improvement in haemodynamics. In addition, blood amitriptyline concentrations were higher in the ILE-treated group. This suggests that either drug absorption from the gastrointestinal-tract was facilitated or drug redistribution was retarded when ILE was given early after oral poisoning.
authors.affiliation: Faculty of Medicine, Department of Pharmacology, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Perichon
authors.forename: S
authors.initials: S
authors.lastname: Turfus
authors.forename: D
authors.initials: D
authors.lastname: Gerostamoulos
authors.forename: A
authors.initials: A
authors.lastname: Graudins
mesh_terms: D000284:Administration, Oral; D000639:Amitriptyline / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000506:poisoning*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000506:poisoning*; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects* / Q000503:physiopathology; D004195:Disease Models, Animal; D062787:Drug Overdose / Q000097:blood / Q000503:physiopathology / Q000628:therapy*; D004655:Emulsions / Q000009:adverse effects / Q000627:therapeutic use; D005217:Fat Emulsions, Intravenous / Q000009:adverse effects* / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007408:Intestinal Absorption; D008297:Male; D010743:Phospholipids / Q000009:adverse effects / Q000627:therapeutic use; D010865:Pilot Projects; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013024:Soybean Oil / Q000009:adverse effects / Q000627:therapeutic use; D016019:Survival Analysis
chemical_list: D000929:Antidepressive Agents, Tricyclic; D004655:Emulsions; D005217:Fat Emulsions, Intravenous; D010743:Phospholipids; C545823:soybean oil, phospholipid emulsion; D000639:Amitriptyline; D013024:Soybean Oil