Bupropion Overdose Resulted in a Pharmacobezoar in a Fatal Bupropion (Wellbutrin^®) Sustained‐release Overdose: Postmortem Distribution of Bupropion and its Major Metabolites

Abstract

Bupropion (BUP) overdose commonly causes generalized seizures and central nervous system depression. The case of a 28-year-old woman who died from a massive lethal overdose with sustained-release bupropion (Wellbutrin 300 mg) is herein presented. The autopsy revealed the presence of a pharmacobezoar consisting of at least 40 tablets in the stomach. Determination of bupropion and its active metabolites (hydroxybupropion, threobupropion, erythrobupropion) was achieved by a liquid chromatographic mass spectrometry (LC-MS/MS) method. Postmortem concentrations for bupropion, hydroxybupropion, threobupropion, and erythrobupropion were obtained in intracranial blood, urine, bile, liver, kidney, and vitreous humor. In this case, intracranial blood level of the parent drug was 1.9 mg/L. Threobupropion was the most abundant metabolite in both blood and urine, 59.3 and 890.6 mg/L. Tissue distribution showed the highest concentration in the liver, 12.3 mg/kg. The 0.8 bupropion concentration ratio vitreous/blood suggested that vitreous could be a valuable specimen for toxicological analysis should postmortem blood be unavailable.

EGD for Refractory Toxidromes: Is It Time to Add to the Algorithm?

“… 6 , 11 This is further supported by unfortunate reports of fatal ingestions that, upon autopsy, found retained medication in the GI tract despite traditional decontamination attempts during resuscitation efforts. 8 …”

“…6,11 This is further supported by unfortunate reports of fatal ingestions that, upon autopsy, found retained medication in the GI tract despite traditional decontamination attempts during resuscitation efforts. 8 A variety of risk factors can predispose to prolonged toxicity: medication formulation, decontamination modalities inand-of themselves, underlying medical disorders, and novel drug delivery techniques. Extended-release medication technology ensures slow release of medications often through outer coatings that are insoluble at lower pH environments.…”

“…Multiple case reports have documented that protracted toxic exposures contribute to significant morbidity and potential mortality. 6 - 8 Compounding this issue, the more common methods of GI decontamination are sometimes ineffective and/or complicate the clinical picture due to unintended side effects. Here, we describe a case of refractory serotonin toxicity that ultimately resolved following endoscopic removal of medication remnants.…”

Death of a Female Prostitute Due to Intestinal Obstruction by an Unknown Substance

“…Bezoars are aggregates of undigested material that are mostly located in the stomach or small intestine; localization in the colon region is extremely rare . Depending on the material, they can be divided into several types: phytobezoars, diospyrobezoars, trichobezoars, and pharmacobezoars .…”

Antemortem and postmortem influences on drug concentrations and metabolite patterns in postmortem specimens

“…In general, modified-release preparations show delayed absorption characteristics followed by delayed clinical effects observed in overdoses (Livshits, Sampson, Howland, Hoffman, & Nelson, 2015). Delayed release may also be caused by formation of so-called pharmacobezoars (England, Heath, Gilbert, & Byard, 2015), that is, specific types of bezoars that occur when pharmaceutical materials, such as tablets, suspensions, and/or drug delivery devices aggregate as it has, for example, been described for bupropion (Schmit, De Boosere, Vanhaebost, & Capron, 2017) or clomipramine (Attou & Reper, 2013) formulations. Another example is a clinical case of severe carbamazepine poisoning with continuously increasing carbamazepine concentrations even after initially decreased serum concentrations (following hemoperfusion).…”