From the FDA Drug Label
12. 3 Pharmacokinetics Bupropion is a racemic mixture. The pharmacologic activity and pharmacokinetics of the individual enantiomers have not been studied. Following chronic dosing, the mean steady-state plasma concentration of bupropion was reached within 8 days. The mean elimination half-life (±SD) of bupropion is 21 (±9) hours
Additionally, in a study comparing 14-day dosing with bupropion hydrochloride extended-release tablets (XL) 300 mg once daily to the sustained-release formulation of bupropion at 150 mg 2 times daily, equivalence was demonstrated for peak plasma concentration and area under the curve for bupropion and the three metabolites
Absorption Following single oral administration of bupropion hydrochloride extended-release tablets (XL) to healthy volunteers, the median time to peak plasma concentrations for bupropion was approximately 5 hours. The presence of food did not affect the peak concentration or area under the curve of bupropion
Distribution In vitro tests show that bupropion is 84% bound to human plasma proteins at concentrations up to 200 mcg/mL.
Metabolism Bupropion is extensively metabolized in humans Three metabolites are active: hydroxybupropion, which is formed via hydroxylation of the tert-butyl group of bupropion, and the amino-alcohol isomers threohydrobupropion and erythrohydrobupropion, which are formed via reduction of the carbonyl group
The pharmacokinetics of Bupropion XL can be described as follows:
- Absorption: The median time to peak plasma concentrations for bupropion is approximately 5 hours.
- Distribution: Bupropion is 84% bound to human plasma proteins at concentrations up to 200 mcg/mL.
- Metabolism: Bupropion is extensively metabolized in humans, with three active metabolites: hydroxybupropion, threohydrobupropion, and erythrohydrobupropion.
- Elimination half-life: The mean elimination half-life of bupropion is 21 (±9) hours.
- Steady-state plasma concentration: The mean steady-state plasma concentration of bupropion is reached within 8 days 1.
From the Research
Bupropion XL has distinct pharmacokinetic properties that make it suitable for once-daily dosing, with a half-life of approximately 21 hours for the parent compound and longer half-lives for its metabolites, as reported in the most recent study 2. The medication reaches peak plasma concentrations approximately 5 hours after administration, with steady-state levels achieved within 8 days of regular dosing. Bupropion undergoes extensive hepatic metabolism, primarily through CYP2B6, producing three active metabolites: hydroxybupropion, threohydrobupropion, and erythrohydrobupropion, as described in 3. Some key points to consider when prescribing bupropion XL include:
- The extended-release formulation provides more consistent plasma levels throughout the day compared to immediate-release versions, reducing side effects and improving adherence.
- Dose adjustments are necessary for patients with hepatic or renal impairment due to reduced clearance, as noted in 4.
- Food can slightly increase the absorption of bupropion XL, but this effect is not clinically significant, allowing the medication to be taken with or without food, typically in the morning to minimize potential sleep disturbances, as reported in 5. It's also worth noting that bupropion XL has been shown to be effective in smoking cessation, particularly in combination with other therapies, as demonstrated in 6 and 2. Overall, bupropion XL is a viable treatment option for patients with major depressive disorder, with its pharmacokinetic properties and efficacy making it a suitable choice for once-daily dosing, as supported by the most recent and highest quality study 2.