CYP2B6 mediates the in vitro hydroxylation of Bupropion ( Wellbutrin SR ): potential drug interactions with other antidepressants.

The in vitro biotransformation of Bupropion ( Wellbutrin SR ) to hydroxyBupropion ( Wellbutrin SR ) was studied in human liver microsomes and microsomes containing heterologously expressed human cytochromes P450 (CYP). The mean (+/-S.E.) K(m) in four human liver microsomes was 89 (+/-14) microM. In microsomes containing cDNA-expressed CYPs, hydroxyBupropion ( Wellbutrin SR ) formation was mediated only by CYP2B6 at 50 microM Bupropion ( Wellbutrin SR ) (K(m) 85 microM). A CYP2B6 inhibitory antibody produced more than 95% inhibition of Bupropion ( Wellbutrin SR ) hydroxylation in four human livers. Bupropion ( Wellbutrin SR ) hydroxylation activity at 250 microM was highly correlated with S-mephenytoin N-demethylation activity (yielding nirvanol), another CYP2B6-mediated reaction, in a panel of 32 human livers (r = 0.94). The CYP2B6 content of 12 human livers highly correlated with Bupropion ( Wellbutrin SR ) hydroxylation activity (r = 0.96). Thus Bupropion ( Wellbutrin SR ) hydroxylation is mediated almost exclusively by CYP2B6 and can serve as an index reaction reflecting activity of this isoform. IC(50) values for inhibition of a CYP2D6 index reaction (dextromethorphan O-demethylation) by Bupropion ( Wellbutrin SR ) and hydroxyBupropion ( Wellbutrin SR ) were 58 and 74 microM, respectively. This suggests a low inhibitory potency versus CYP2D6, the clinical importance of which is not established. Since Bupropion ( Wellbutrin SR ) is frequently coadministered with other antidepressants, IC(50) values (microM) for inhibition of Bupropion ( Wellbutrin SR ) hydroxylation were determined as follows: Paroxetine ( Paxil ) (1.6), fluvoxamine (6.1), Sertraline HCL ( Zoloft )(3.2), desmethylSertraline HCL ( Zoloft )(19.9), Fluoxetine ( Prozac ) (59.5), norFluoxetine ( Prozac ) (4.2), and nefazodone (25.4). Bupropion ( Wellbutrin SR ) hydroxylation was only we


To investigate the cause of chest pain during the use of Bupropion ( Wellbutrin SR ) as an aid to stop smoking. METHODS: The Netherlands Pharmacovigilance Centre received 22 reports of chest pain, associated with the use of Bupropion ( Wellbutrin SR ) as an aid to smoking cessation. Additional information about long-term follow up was collected to analyze whether these complaints herald manifest cardiac disease. RESULTS: All but one patient recovered after withdrawal of Bupropion ( Wellbutrin SR ). Seven patients were additionally investigated and in six of them, a cardiac cause could be excluded. During long-term follow-up, no coronary heart diseases were diagnosed. CONCLUSIONS: These reports indicate that chest pain seems to be associated with the use of Bupropion ( Wellbutrin SR ), but its origin remains unclear.

Effect of plasma from patients containing Bupropion ( Wellbutrin SR ) and its metabolites on the uptake of norepinephrine.

The uptake of norepinephrine into cortical punches from the brain of the rat was studied in the presence of buffer and plasma from patients containing Bupropion ( Wellbutrin SR ) and its metabolites. Even though Bupropion ( Wellbutrin SR ) and its metabolite (compound II) were equipotent in inhibiting the uptake of NE in buffer, compound II was twice as active as Bupropion ( Wellbutrin SR ) in the presence of human plasma. When the inhibition of uptake of NE in the presence of plasma, obtained from patients on Bupropion ( Wellbutrin SR ) on steady-state, was correlated with levels of Bupropion ( Wellbutrin SR ) and its metabolites (II, III, IV) a highly significant correlation was seen in the presence of compound II. Since this compound accumulated in plasma from patients 20-100 times that of the parent compound, the mode of action of Bupropion ( Wellbutrin SR ) may in part be due to the effect of this compound on the uptake of NE.

Use of Bupropion ( Wellbutrin SR ) SR in a pharmacist-managed outpatient smoking-cessation program.

We administered Bupropion ( Wellbutrin SR ) sustained-release (SR) in a pharmacist-managed outpatient smoking-cessation program. Patients were referred to the program by their primary care physician. All patients completed initial visit questionnaires, received behavioral counseling by a clinical pharmacist, and were provided educational materials on smoking cessation. Seventy-one patients received Bupropion ( Wellbutrin SR ) SR for treatment of nicotine dependence and were followed for 6 months. Point prevalence abstinence rates were 28.2% and 25.4% at 8 weeks and 6 months, respectively. The trend was toward lower cessation rates in patients with a documented psychiatric diagnosis at 6 months (p=0.064). Bupropion ( Wellbutrin SR ) SR was fairly well tolerated, with the most common adverse effects being dry mouth and bad taste. The agent appears to have better success for smoking cessation in patients free of psychiatric comorbidities, but further research is required to support this finding.