ArticleDrug metabolism and disposition: the biological fate of chemicals2016
Stereoselective Metabolism of Bupropion to OH-bupropion, Threohydrobupropion, Erythrohydrobupropion, and 4'-OH-bupropion in vitro.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 43 citations in OpenAlex.
- Pharmacogenetic Influence on Stereoselective Steady-State Disposition of Bupropion.Drug metabolism and disposition: the biological fate of chemicals · 2024Trial
- Common Polymorphisms of CYP2B6 Influence Stereoselective Bupropion Disposition.Clinical pharmacology and therapeutics · 2019Trial
- Pharmacokinetics and Pharmacogenomics of Bupropion in Three Different Formulations with Different Release Kinetics in Healthy Human Volunteers.The AAPS journal · 2017Trial
- Physiologically Based Pharmacokinetic Modeling to Assess Perpetrator and Victim Cytochrome P450 2C Induction Risk.Pharmaceutics · 2025Article
- The strong clinical interaction between bupropion and CYP2D6 is primarily mediated through bupropion metabolites and their stereoisomers: A paradigm for evaluating metabolites in drug-drug interaction risk.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Evaluation of reversible cytochrome P450 inhibition by Withania somnifera leaf and root extracts.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
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- Bupropion decreases plasma levels of asymmetric dimethylarginine and ameliorates renal injury by modulation of Ddah1, Oatp4c1, Oct2, and Mate1 in rats with adenine-induced chronic renal injury.Frontiers in pharmacology · 2025Article
- Metabolite Measurement in Index Substrate Drug Interaction Studies: A Review of the Literature and Recent New Drug Application Reviews.Metabolites · 2024Review
- INTEDE 2.0: the metabolic roadmap of drugs.Nucleic acids research · 2024Article
- Characterization of the Stereoselective Disposition of Bupropion and Its Metabolites in Rat Plasma and Brain.European journal of drug metabolism and pharmacokinetics · 2023Article
- Stereoselective Metabolism of Bupropion to Active Metabolites in Cellular Fractions of Human Liver and Intestine.Drug metabolism and disposition: the biological fate of chemicals · 2023Article
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- Candidate Proficiency Test Chemicals to Address Industrial Chemical Applicability Domains forFrontiers in toxicology · 2022Review
- A Bayesian population physiologically based pharmacokinetic absorption modeling approach to support generic drug development: application to bupropion hydrochloride oral dosage forms.Journal of pharmacokinetics and pharmacodynamics · 2021Article
- Physiologically Based Pharmacokinetic Modeling of Bupropion and Its Metabolites in a CYP2B6 Drug-Drug-Gene Interaction Network.Pharmaceutics · 2021Article
- Characterization of the Effect of Upadacitinib on the Pharmacokinetics of Bupropion, a Sensitive Cytochrome P450 2B6 Probe Substrate.Clinical pharmacology in drug development · 2021Article
- Population model analysis of chiral inversion and degradation of bupropion enantiomers, and application to enantiomer specific fraction unbound determination in rat plasma and brain.Journal of pharmaceutical and biomedical analysis · 2021Article
- Mechanistic PBPK Modeling of Urine pH Effect on Renal and Systemic Disposition of Methamphetamine and Amphetamine.The Journal of pharmacology and experimental therapeutics · 2020Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Bupropion is a widely used antidepressant, smoking cessation aid, and weight-loss therapy. It is administered as a racemic mixture, but the pharmacokinetics and activity of bupropion are stereoselective. The activity and side effects of bupropion are attributed to bupropion and its metabolites S,S- and R,R-OH-bupropion, threohydrobupropion, and erythrohydrobupropion. Yet the stereoselective metabolism in vitro and the enzymes contributing to the stereoselective disposition of bupropion have not been characterized. In humans, the fraction of bupropion metabolized (fm) to the CYP2B6 probe metabolite OH-bupropion is 5-16%, but ticlopidine increases bupropion exposure by 61%, suggesting a 40% CYP2B6 and/or CYP2C19 fm for bupropion. Yet, the CYP2C19 contribution to bupropion clearance has not been defined, and the enzymes contributing to overall bupropion metabolite formation have not been fully characterized. The aim of this study was to characterize the stereoselective metabolism of bupropion in vitro to explain the stereoselective pharmacokinetics and the effect of drug-drug interactions (DDIs) and CYP2C19 pharmacogenetics on bupropion exposure. The data predict that threohydrobupropion accounts for 50 and 82%, OH-bupropion for 34 and 12%, erythrohydrobupropion for 8 and 4%, and 4'-OH-bupropion for 8 and 2% of overall R- and S-bupropion clearance, respectively. The fm,CYP2B6 was predicted to be 21%, and the fm,CYP2C19, 6% for racemic bupropion. Importantly, ticlopidine was found to inhibit all metabolic pathways of bupropion in vitro, including threohydrobupropion, erythrohydrobupropion, and 4'OH-bupropion formation, explaining the in vivo DDI. The stereoselective pharmacokinetics of bupropion were quantitatively explained by the in vitro metabolic clearances and in vivo interconversion between bupropion stereoisomers.
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