Hydroxybupropion

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Hydroxybupropion
Clinical data
Other namesBW 306U; 6-Hydroxybupropion
ATC code
  • None
Pharmacokinetic data
Elimination half-life15–25 hours
Identifiers
  • (±)-1-(3-Chlorophenyl)-2-[(1-hydroxy-2-methyl-2-propanyl)amino]-1-propanone
JSmol)
  • O=C(c1cc(Cl)ccc1)C(NC(C)(C)CO)C
  • InChI=1S/C13H18ClNO2/c1-9(15-13(2,3)8-16)12(17)10-5-4-6-11(14)7-10/h4-7,9,15-16H,8H2,1-3H3
  • Key:AKOAEVOSDHIVFX-UHFFFAOYSA-N

Hydroxybupropion (code name BW 306U), or 6-hydroxybupropion, is the major

first-pass metabolism.[1] With oral bupropion treatment, hydroxybupropion is present in plasma at area under the curve concentrations that are as many as 16–20 times greater than those of bupropion itself,[1][2] demonstrating extensive conversion of bupropion into hydroxybupropion in humans.[1] As such, hydroxybupropion is likely to play a very important role in the effects of oral bupropion, which could accurately be thought of as functioning largely as a prodrug to hydroxybupropion.[1] Other metabolites of bupropion besides hydroxybupropion include threohydrobupropion and erythrohydrobupropion.[3][4]

Pharmacology

Pharmacology of bupropion and its metabolites.
  Bupropion R,R-
Hydroxy
bupropion 		S,S-
Hydroxy
bupropion 		Threo-
hydro
bupropion 		Erythro-
hydro
bupropion
Exposure and half-life
AUC relative
to bupropion[5][6] 		1 23.8 0.6 11.2 2.5
Half-life[7] 11 h 19 h 15 h 31 h 22 h
Inhibition IC50 (μM) in human cells, unless noted otherwise
DAT, uptake[8] 0.66 inactive 0.63 47 (rat)[9] no data
NET, uptake[8] 1.85 9.9 0.24 16 (rat)[9] no data
SERT, uptake[8] inactive inactive inactive 67 (rat)[9] no data
α3β4 nicotinic[8] 1.8 6.5 11 14 (rat)[10] no data
α4β2 nicotinic[11] 12 31 3.3 no data no data
α1β1γδ nicotinic[11] 7.9 7.6 28 no data no data

Pharmacodynamics

Compared to bupropion, hydroxybupropion is similar in its

non-competitive antagonist of nACh receptors, such as α4β2 and α3β4, but is even more potent in comparison.[1][11][12][13][14]

Pharmacokinetics

Bupropion is extensively and rapidly absorbed in the gastrointestinal tract but experiences extensive first pass metabolism rendering its systemic bioavailability limited. Exact bioavailability has yet to be determined given an intravenous form does not exist. Absorption is suggested to be between 80 and 90%.[15][16] Its distribution half-life is between 3–4 hours and exhibits moderate human plasma protein binding (between 82 and 88%) with the parent compound and hydroxybupropion displaying the highest affinity.[17][4] Bupropion is a racemic mixture and is metabolized hepatically primarily via oxidative cleavage of its side chains by CYP2B6. Hydroxybupropion is the most potent of the metabolites. It is formed via the "hydroxylation of the tert-butyl group" by CYP2B6 and is excreted renally.[17] Cmax values of hydroxybupropion are 4–7 times that of bupropion, while the exposure to hydroxybupropion is "10 fold" that of bupropion. Hydroxybupropion's elimination half-life is roughly 20 hours, give or take 5 hours and will reach steady state concentrations within 8 days.[17][4]

Chemistry

Hydroxybupropion is a racemic mixture of (R,R)-hydroxybupropion and (S,S)-hydroxybupropion.

Research

Although there are patents proposing uses and formulations of this compound, hydroxybupropion is not currently marketed as a drug in and of itself and is only available for use in non-clinical research. Hydroxybupropion is not a scheduled drug or a controlled substance.[18] One can access GLP (Good Lab Practice) documents detailing assays/techniques to further research and isolate this drug.[19][20] Otherwise, there is little regulatory data available for hydroxybupropion at this time. Moreover, there is little information to suggest hydroxybupropion has an abuse potential. However, it has been studied as a possible therapeutic for alcohol and nicotine use as a codrug.[21]

There are few clinical trials or toxicology studies assessing hydroxybupropion alone at this time. There are clinical studies which assess hydroxybupropion in conjunction with bupropion suggesting hydroxybupropion to be the primary form of the compound responsible for its clinical efficacy.[22][12] Also, transdermal delivery of bupropion and hydroxybupropion has been assessed finding bupropion to be the superior candidate given its elevated diffusion rate through skin samples.[23] There are few toxicology studies assessing hydroxybupropion alone at this time. However, there are some studies which assess this compound in conjunction with others or its parent compound.

See also

  • Radafaxine – a cyclised derivative of hydroxybupropion
  • Manifaxine – an analogue of radafaxine and hydroxybupropion

References

  1. ^
    ISBN 978-0-12-420177-4. Archived
    from the original on 4 June 2020. Retrieved 25 October 2016.
  2. ISBN 978-1-60913-345-0. Archived
    from the original on 11 December 2021. Retrieved 25 October 2016.
  3. S2CID 163167323
    .
  4. ^
    PMID 16368442
    .
  5. PMID 30460996
    .
  6. S2CID 218563059
    .
  7. PMID 27255113
    .
  8. ^
    PMID 20509659
    .
  9. ^
    S2CID 19490821
    .
  10. PMID 12909199
    .
  11. ^
    S2CID 1577336
    .
  12. ^
    PMID 23149928
    .
  13. ISBN 978-1-4939-0986-5. Archived
    from the original on 20 March 2017. Retrieved 25 October 2016.
  14. ISBN 978-1-4419-0338-9. Archived
    from the original on 27 April 2021. Retrieved 25 October 2016.
  15. S2CID 195687060
    .
  16. ^ "Bupropion, CID 62889". PubChem. National Center for Biotechnology Information.
  17. ^ a b c "Bupropion hydrochloride Tablets" (PDF). Glaxosmithkline. 2004. Archived from the original (PDF) on 2017-05-16.
  18. ^ "Orangebook, Lists of: Scheduling Actions Controlled Substances Regulated Chemicals" (PDF). Drug and Chemical Evaluation Section Office of Diversion Control Drug Enforcement Administration. U.S. Department of Justice. Archived from the original (PDF) on 2016-04-17.
  19. S2CID 8789343
    .
  20. PMID 17656162
    .
  21. PMID 16798000
    .
  22. PMID 24484978
    .
  23. PMID 18623203
    .
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