hydroxybupropion hydroxybupropion hydroxybupropion (code name bw 306u), or 6-hydroxybupropion, is the major active metabolite of the antidepressant and smoking cessation drug bupropion. it is formed from bupropion by the liver enzyme cyp2b6 during first-pass metabolism. 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, demonstrating extensive conversion of bupropion into hydroxybupropion in humans. 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. other metabolites of bupropion besides hydroxybupropion include threohydrobupropion and erythrohydrobupropion. hydroxybupropionclinical dataother namesbw 306u; 6-hydroxybupropionatc codenonepharmacokinetic dataelimination half-life15–25 hoursidentifiers iupac name (±)-1-(3-chlorophenyl)-2--1-propanone cas number357399-43-0 ypubchem cid446chemspider433uniiv94f513635chebichebi:166487chemblchembl3544616comptox dashboard (epa)dtxsid101002894 chemical and physical dataformulac13h18clno2molar mass255.74 g·mol−13d model (jsmol)interactive image smiles o=c(c1cc(cl)ccc1)c(nc(c)(c)co)c inchi 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,8h2,1-3h3key:akoaevosdhivfx-uhfffaoysa-n pharmacology pharmacology of bupropion and its metabolites. bupropion r,r-hydroxybupropion s,s-hydroxybupropion threo-hydrobupropion erythro-hydrobupropion exposure and half-life auc relativeto bupropion 1 23.8 0.6 11.2 2.5 half-life 11 h 19 h 15 h 31 h 22 h inhibition ic50 (μm) in human cells, unless noted otherwise dat, uptake 0.66 inactive 0.63 47 (rat) no data net, uptake 1.85 9.9 0.24 16 (rat) no data sert, uptake inactive inactive inactive 67 (rat) no data α3β4 nicotinic 1.8 6.5 11 14 (rat) no data α4β2 nicotinic 12 31 3.3 no data no data α1β1γδ nicotinic 7.9 7.6 28 no data no data pharmacodynamics compared to bupropion, hydroxybupropion is similar in its potency as a norepinephrine reuptake inhibitor (ic50 = 1.7 μm), but is substantially weaker as a dopamine reuptake inhibitor (ic50 = >10 μm). like bupropion, hydroxybupropion is also a non-competitive antagonist of nach receptors, such as α4β2 and α3β4, but is even more potent in comparison. 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 80-90%. its distribution half-life is between 3–4 hours and exhibits moderate human plasma protein binding (between 82–88%) with the parent compound and hydroxybupropion displaying the highest affinity. 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. cmax vales 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. 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, hydroxybuproprion 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. one can access glp (good lab practice) documents detailing assays/techniques to further research and isolate this drug. 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. 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. 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. 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.