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Bupropion

What the body does with Bupropion, from the dose to the exit, as its Wikipedia drug infobox records it.

Quoted from the Wikipedia infobox, not yet written up by hand. The order is the usual order of events, not a measured schedule.

The three routes out of the dose

Bupropion is given as a 50:50 mix of its two mirror forms. The liver splits it three ways. The multiples are each metabolite's blood exposure compared with bupropion itself. 234

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THE BUPROPION METABOLIC LANDSCAPE A Comprehensive Breakdown of Pathways, Steady-State Exposure, and Molecular Targets 1. METABOLIC FLOW & ENZYMATIC BIO-TRANSFORMATION ORAL BUPROPION Given as Racemate | Only ~0.5% Unchanged t-BUTYL HYDROXYLATION CARBONYL REDUCTION CARBONYL REDUCTION HYDROXYBUPROPION Steady-State: ~10–13× Parent Enzyme: CYP2B6 Favors R,R-enantiomer bioactivation Primary Target Mechanism: Norepinephrine & Dopamine Reuptake Inhibition (NDRI) THREOHYDROBUPROPION Steady-State: ~7× Parent Enzyme: 11β-HSD1 Stereoselectively converts R-bupropion Primary Target Mechanism: α₃β₄ Nicotinic Acetylcholine Receptor Antagonism (Smoking Cessation) ERYTHROHYDROBUPROPION Steady-State: ~1.4× Parent Enzyme: CBR1 / AKR1C1-3 Microsomal reductases (Non-11β-HSD1) Primary Target Mechanism: Weak NDRI Pathway; Alters seizure thresholds in animal models 2. PHARMACOGENETIC & STRUCTURAL HOTSPOTS The Genetic Bottleneck: CYP2B6*6 Carriers of *6: [5] Hydroxybupropion exposure runs about 23% lower than in non-carriers; parent plus metabolite about 19% lower. The Clearance Paradox: [6] Changes in CYP2B6 activity shift the active metabolite a lot, but bupropion's own blood levels barely move. Stereoselectivity Asymmetric Kinetics: [7] Given as a 50:50 racemate, but the metabolism is stereo- selective, giving a set of mirror-form metabolites. Functional Allocation: [7][6] CYP2B6 makes R,R-hydroxybupropion, the better marker of CYP2B6 activity. Low CYP2C19 raises the reduced metabolites. 3. CLINICAL CONSEQUENCES & DRUG-DRUG INTERACTIONS CYP2D6 Downregulation [8] Bupropion and its metabolites turn down CYP2D6 mRNA as well as blocking the enzyme directly. Together these explain the size of the interaction seen in people. R,R-hydroxybupropion and threohydrobupropion each block about 86% of CYP2D6 activity in the body. [7] Kidney and Liver Shifts In 8 haemodialysis patients on a single 150 mg dose, bupropion itself looked normal but the metabolites built up. The authors suggested 150 mg every 3 days, not daily. [9] Bupropion is contraindicated in severe liver cirrhosis. Small, single-dose studies: treat the numbers as rough. [10] Sources 1-10 are listed below this diagram.

The clock, on a log scale

Each bar runs from the dose to about five half-lives, roughly when 97% of that molecule has been converted or cleared. The scale is logarithmic so minutes and days fit on one line.

  1. doseabsorbed

    Bioavailability

    Unknown 1

  2. hoursbreakdown

    Metabolism

    Liver, intestines (CYP2B6, others) 1

  3. hoursmade from it

    Metabolites

    Hydroxybupropion; Threohydrobupropion; Erythrohydrobupropion; Others 1

  4. half-lifehalf gone

    Elimination half-life

    Bupropion: alpha: 0.5–1.04; beta: 11 h; Hydroxybupropion: 20 h; Threohydrobupropion: 37 h; Erythrohydrobupropion: 33 h 1

Source

  1. Wikipedia, Bupropion, drug infobox (revision 1377736670), CC BY-SA 4.0. Values quoted as they appear, with wiki markup removed.
  2. Kharasch ED, Mitchell D, Coles R. Stereoselective bupropion hydroxylation as an in vivo phenotypic probe for CYP2B6 activity. J Clin Pharmacol 2008;48(4):464-74 (PubMed 18287571).
  3. Skarydova L et al. Deeper insight into the reducing biotransformation of bupropion in the human liver. Drug Metab Pharmacokinet 2014;29(2):177-84 (PubMed 24088726).
  4. Connarn JN et al. Metabolism of bupropion by carbonyl reductases in liver and intestine. Drug Metab Dispos 2015;43(7):1019-27 (PubMed 25904761).
  5. Eum S et al. Association of CYP2B6 genetic polymorphisms with bupropion and hydroxybupropion exposure: a systematic review and meta-analysis. Pharmacotherapy 2022;42(1):34-44 (PubMed 34752647). Ratio of means 0.77 for hydroxybupropion and 0.81 for the active moiety in CYP2B6*6 carriers.
  6. Zhu AZX et al. Gene variants in CYP2C19 are associated with altered in vivo bupropion pharmacokinetics but not bupropion-assisted smoking cessation outcomes. Drug Metab Dispos 2014;42(11):1971-7 (PubMed 25187485).
  7. Dash RP, Rais R, Srinivas NR. Chirality and neuropsychiatric drugs: an update on stereoselective disposition and clinical pharmacokinetics of bupropion. Xenobiotica 2018;48(9):945-57 (PubMed 28876959).
  8. Sager JE et al. In vitro to in vivo extrapolation of the complex drug-drug interaction of bupropion and its metabolites with CYP2D6; simultaneous reversible inhibition and CYP2D6 downregulation. Biochem Pharmacol 2017;123:85-96 (PubMed 27836670).
  9. Worrall SPR, Almond MK, Dhillon S. Pharmacokinetics of bupropion and its metabolites in haemodialysis patients who smoke. A single dose study. Nephron Clin Pract 2004;97(3):c83-9 (PubMed 15292684). Eight patients, single dose.
  10. West R. Bupropion SR for smoking cessation. Expert Opin Pharmacother 2003;4(4):533-40 (PubMed 12667116).

Half-lives vary between people, doses and routes. This page explains what the body does with a drug. It is not dosing advice.