In accordance with its low DAT occupancy, no measurable dopamine release in the human brain was detected with bupropion (one 150 mg dose) in a PET study. These findings raise questions about the role of dopamine reuptake inhibition in the pharmacology of bupropion, and suggest that other actions may be responsible for its therapeutic effects. More research is needed in this area. No data are available on occupancy of the norepinephrine transporter (NET) by bupropion and its metabolites. However, due to the increased exposure of hydroxybupropion over bupropion itself, which has higher affinity for the NET than the DAT, bupropions overall pharmacological profile in humans may end up making it effectively more of a norepinephrine reuptake inhibitor than a dopamine reuptake inhibitor. Accordingly, the clinical effects of bupropion are more consistent with noradrenergic activity than with dopaminergic actions. Pharmacokinetics
After oral administration, bupropion is rapidly and completely absorbed reaching the peak blood plasma concentration after 1.5 hours (tmax). Sustained release (SR) and extended release (XL) formulations have been designed to slow down absorption resulting in tmax of 3 hours and 5 hours, respectively. Absolute bioavailability of bupropion is unknown but is presumed to be low, at 5–20%, due to the first-pass metabolism. As for the relative biovailability of the formulations, XL formulation has lower bioavailability (68%) compared to SR formulation and immediate release bupropion.Bupropion is metabolized in the body by a variety of pathways. The oxidative pathways are by cytochrome P450 isoenzymes CYP2B6 leading to R,R- and S,S-hydroxybupropion and, to a lesser degree, CYP2C19 leading to 4-hydroxybupropion.
It was approved by the U.S. Food and Drug Administration (FDA) as an antidepressant on 30 December 1985, and marketed under the name Wellbutrin. However, a significant incidence of seizures at the originally recommended dosage (400–600 mg/day) caused the withdrawal of the drug in 1986. Subsequently, the risk of seizures was found to be highly dose-dependent, and bupropion was re-introduced to the market in 1989 with a lower maximum recommended daily dose of 450 mg/day.In 1996, the FDA approved a sustained-release formulation of alcohol-resistant bupropion called Wellbutrin SR, intended to be taken twice a day (as compared with three times a day for immediate-release Wellbutrin). In 2003, the FDA approved another sustained-release formulation called Wellbutrin XL, intended for once-daily dosing. Wellbutrin SR and XL are available in generic form in the United States and Canada. In 1997, bupropion was approved by the FDA for use as a smoking cessation aid under the name Zyban. In 2006, Wellbutrin XL was similarly approved as a treatment for seasonal affective disorder.In France, marketing authorization was granted for Zyban on 3 August 2001, with a maximum daily dose of 300 mg; only sustained-release bupropion is available, and only as a smoking cessation aid.On 11 October 2007, two providers of consumer information on nutritional products and supplements, ConsumerLab.com and The Peoples Pharmacy, released the results of comparative tests of different brands of bupropion. The Peoples Pharmacy received multiple reports of increased side effects and decreased efficacy of generic bupropion, which prompted it to ask ConsumerLab.com to test the products in question.