Reply to: Treatment of Bupropion Toxicity with Lipid Emulsion

We thank the authors for these clinically important observations relating to the management of acute drug-related toxicity with intravenous lipid emulsion (ILE), particularly their discussion of laboratory data to discuss kinetics of the pharmacologic agents in the case presented.[1]

Dr. Lee and Dr. Sohn note astutely that the recurrence of symptomatology following initial treatment of bupropion overdose with ILE in the presented case may have resulted from expected pharmacokinetics of ILE, namely, its short half-life of 13.7 ± 5.2 minutes.[2] Indeed, it is well understood that ILE is rapidly removed from the bloodstream into the hepatobiliary system.[3] Per the medication package insert, the plasma elimination half-life of bupropion extended release is 21 (±9) hours, though this is a referent from chronic dosing and not in the context of overdose.[4] Case report literature notes a slightly shorter (19.8 hours) elimination half-life in patients with significant acute overdose.[5] However, even this shorter half-life does not account for the discrepancy in plasma kinetics considering the bolus (versus continuous infusion) dosing of ILE. Drs. Lee and Sohn present a strong argument for the alternative mechanism of action of ILE that accounts for the discrepancy in plasma kinetics, for example, lipid shuttle.

We agree that further research is needed to confirm this lipid-shuttle mechanism with in vivo studies. However, this remains challenging due to (1) the paucity of overdose cases, particularly cases in which serum drug levels are obtained, reported, and/or published; and (2) extended ethical dilemmas in studying acute overdose, particularly in pediatric populations in extremis.

• References

• 1 French D, Smollin C, Ruan W, Wong A, Drasner K, Wu AH. Partition constant and volume of distribution as predictors of clinical efficacy of lipid rescue for toxicological emergencies. Clin Toxicol (Phila) 2011; 49 (09) 801-809
• 2 Cohen JC. Chylomicron triglyceride clearance: comparison of three assessment methods. Am J Clin Nutr 1989; 49 (02) 306-313
• 3 Rössner S. Further methodological studies on the intravenous fat tolerance with Intralipid emulsion. Scand J Clin Lab Invest 1976; 36 (02) 155-159
• 4 Highlights of prescribing information for WELLBUTRIN SR. Available at: https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Wellbutrin_SR/pdf/WELLBUTRIN-SR-PI-MG.PDF . Accessed February 3, 2020
• 5 Donnelly K, Walkowiak HB, Donnelly C, Jenkinson E, Rizkalla J, Langford N. Bupropion toxicokinetic: a case report. Clin Toxicol (Phila) 2010; 48 (04) 385-387