Clinical data | |
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Other names | (R,R)-Hydroxybupropion |
Pharmacokinetic data | |
Metabolism | Glucuronidation[1][2] |
Metabolites | Hydroxybupropion glucuronide[1][2] |
Elimination half-life | 19–26 hours[1][2] |
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CAS Number | |
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ChemSpider | |
ChEMBL | |
CompTox Dashboard (EPA) | |
Chemical and physical data | |
Formula | C13H18ClNO2 |
Molar mass | 255.74 g·mol−1 |
3D model (JSmol) | |
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(2R,3R)-Hydroxybupropion, or simply (R,R)-hydroxybupropion, is the major metabolite of the antidepressant, smoking cessation, and appetite suppressant medication bupropion.[3][4][1][5] It is the (2R,3R)-enantiomer of hydroxybupropion, which in humans occurs as a mixture of (2R,3R)-hydroxybupropion and (2S,3S)-hydroxybupropion (radafaxine).[4][5] Hydroxybupropion is formed from bupropion mainly by the cytochrome P450 enzyme CYP2B6.[4][1][2] Levels of (2R,3R)-hydroxybupropion are dramatically higher than those of bupropion and its other metabolites during bupropion therapy.[4][2][5]
The hydroxylation of bupropion to form hydroxybupropion occurs by cytochrome P450 2B6 (CYP2B6) oxidation (Faucette et al., 2000; Faucette, Hawke, Shord, Lecluyse, & Lindley, 2001; Hesse et al., 2000), and the subsequent cyclization results in the creation of a second chiral center with the potential for the generation of two diastereomers (Suckow, Zhang, & Cooper, 1997). Interestingly, only the trans-diastereomers, (2S,3S)- and (2R,3R)-hydroxybupropion (2a and 2b, respectively), have been found in plasma in humans and when synthesized de novo (Fang et al., 2000), indicating that they are the thermodynamically more stable isomers. Steric hindrance greatly reduces cyclization to the cis-diastereomers, (2R,3S)- and (2S,3R)-hydroxybupropion (Suckow et al., 1997). The chirality of the second stereocenters is determined by the configuration of the existing stereocenter alpha to the ketone derived from either (S)- or (R)- bupropion.
KharaschNeinerKraus2020
was invoked but never defined (see the help page).