Bupropion is an anti-depressant and smoking cessation drug taken orally. It is digested in the stomach and intestine where bupropion is transported out of the the intestine through the epithelial cells through an unknown transport. In the blood it travels to the liver where it is transported into the live through an unknown transport protein. Bupropion is not transported by any major hepatic transporters. On the endoplasmic reticulum in the liver, bupropion is metabolized into Hydroxybupropion by the enzyme Cytochrome P450 2B6, threohydrobupropion by the enzyme 11β-HSD1, and erythrohydrobupropion by a carbonyl reductase enzyme. Hydroxybupropion, threohydrobupropion, and erythrohydrobupropion are all active metabolites of bupropion. Threohydrobupropion and erythrohydrobupropion are very similar metabolites with only a different bond in their structure of the compounds. Hydroxybupropion has been shown to have the same affinity for norepinephrine reuptake transporters, but only 50% of the anti-depressant effects of bupropion. Bupropion is also metabolized into the inactive metabolites (2R)-1-(3-chlorophenyl)-2-[(1-hydroxy-2-methylpropan-2-yl)amino]propan-1-one by the enzymes Cytochrome P450 2B6 or Cytochrome P450 3A4; (2R)-2-(tert-butylamino)-1-(3-chlorophenyl)-3-hydroxypropan-1-one by the enzymes Cytochrome P450 2C19, Cytochrome P450 2B6, or Cytochrome P450 2E1; and (2R)-2-(tert-butylamino)-1-(3-chloro-5-hydroxyphenyl)propan-1-one by the enzymes Cytochrome P450 2B6 or Cytochrome P450 2E1. All of these metabolites are transported out of the liver into the blood vessels or bile by unknown transport proteins. The elimination of the metabolites happens mainly in the kidneys where 87% of the dose is renally excreted. 10% of the dose is excreted fecally through bile to the intestines. 0.5% of the dose is excreted as unchanged bupropion.

Bupropion Metabolism References