Pharmacokinetic and pharmacodynamic of bupropion: integrative overview of relevant clinical and forensic aspects

Abstract

Bupropion is an atypical antidepressant of the aminoketone group, structurally related to cathinone, associated with a wide interindividual variability. An extensive pharmacokinetic and pharmacodynamic review of bupropion was performed, also focusing on chemical, pharmacological, toxicological, clinical and forensic aspects of this drug without a limiting period. Bupropion is a chiral, basic, highly lipophilic drug, clinically used as racemate that undergoes extensive stereoselective metabolism. Its major active metabolites, hydroxybupropion, threohydrobupropion, and erythrohydrobupropion reach higher plasma concentrations than bupropion. Bupropion exerts its effects mainly by inhibiting dopamine and norepinephrine reuptake and by blocking several nicotinic receptors. Recent reports highlight recreational use of bupropion via intranasal insufflation and intravenous use. Seizures, insomnia, agitation, headache, dry mouth, and nausea are some of the reported adverse effects. Neurologic effects are major signs of intoxication that should be carefully managed. Finally, the characterization of the polymorphic enzymes involved in the metabolism of bupropion is essential to understand factors that may influence the interindividual and intraindividual variability in bupropion metabolite exposure, including the evaluation of potential drug–drug interactions and pharmacogenetic implications.

Keywords:

• Bupropion
• pharmacokinetics
• metabolism
• pharmacodynamics
• polymorphisms
• forensic and clinical aspects

Disclosure statement

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received, or pending or royalties. No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported by grants from CESPU (TramTap-CESPU-2016, Chronic-TramTap_CESPU_2017 and TraTapMDMA-CESPU-2018) and Fundação para a Ciência e a Tecnologia (UID/DTP/04138/2013).