J Chromatogr B Analyt Technol Biomed Life Sci. 2004 May 25;804(2):277-87.
High-throughput liquid chromatography-tandem mass spectrometry determination of bupropion and its metabolites in human, mouse and rat plasma using a monolithic column.

Borges V, Yang E, Dunn J, Henion J.

Analytical Toxicology, Department of Population Medicine and Diagnostic Sciences, Cornell University, 927 Warren Drive, Ithaca, NY 14850, USA.

In the present work, a high-throughput LC/MS/MS method using a Chromolith RP-18 ( [Formula: see text] mm) monolithic column was developed and partially validated for the determination of bupropion (BUP), an anti-depressant drug, and its metabolites, hydroxybupropion and threo-hydrobupropion (TB), in human, mouse, and rat plasma. A modern integrated liquid chromatograph and an LC/MS/MS system with a TurboIonSpray (TIS) interface were used for the positive electrospray selected reaction monitoring (SRM) LC/MS analyses. Spiked control plasma calibration standards and quality control (QC) samples were extracted by semi-automated 96-well liquid-liquid extraction (LLE) using ethyl acetate. A mobile phase consisting of 8mM ammonium acetate-acetonitrile (55:45, v/v) delivered isocratically at 5ml/min, and split post-column to 2ml/min directed to the TIS, provided the optimum conditions for the chromatographic separation of bupropion and its metabolites within 23s. The isotope-labeled D(6)-bupropion and D(6)-hydroxybupropion were used as internal standards. The method was linear over a concentration range of 0.25-200ng/ml (bupropion and threo-hydrobupropion), and 1.25-1000ng/ml (hydroxybupropion). The intra- and inter-day assay accuracy and precision were within 15% for all analytes in each of the biological matrices. The monolithic column performance as a function of column backpressure, peak asymmetry, and retention time reproducibility was adequately maintained over 864 extracted plasma injections.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15081921&dopt=Abstract Bupropion Wellbutrin




Pharmacogenetics. 2004 Apr;14(4):225-238.
Pharmacogenetic determinants of interindividual variability in bupropion hydroxylation by cytochrome P450 2B6 in human liver microsomes.

Hesse LM, He P, Krishnaswamy S, Hao Q, Hogan K, Moltke LL, Greenblatt DJ, Court MH.

Clinical Pharmacology Laboratory and Comparative and Molecular Pharmacogenetics Laboratory, Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts and Department of Anaesthesiology, University of Wisconsin Medical School, Madison, Wisconsin, USA.

Bupropion is primarily metabolized in human liver by cytochrome P450 (CYP) 2B6, an isoform that shows high interindividual variability in expression and catalysis. The aim of this study was to identify mechanisms underlying this variability through comprehensive phenotype-genotype analysis of a well-characterized human liver bank (n = 54). There was substantial variability in microsomal bupropion hydroxylation activities (over 45-fold) and CYP2B6 protein content (over 288-fold), with excellent correlation between protein and activity values (rs = 0.88). CYP2B6 mRNA levels showed less variability (13-fold) and poorer correlation (rs = 0.44) to CYP2B6 protein resulting from 20-30% of livers that contained substantial CYP2B6 mRNA, but low CYP2B6 protein. Livers were genotyped for the common coding polymorphisms (Q172H, K262R and R487C) and 14 additional variations identified by sequencing of the gene promoter to -3000 bp. Of 14 haplotypes that were inferred, *1A (reference), *1H (-2320t>c; -750t>c) and *6B (-1456t>c; -750t>c; Q172H; K262R) were most common with frequencies of 0.28, 0.20 and 0.26, respectively. Alcohol use history (P = 0.011) and *6B haplotype (P = 0.011) were identified as significant predictors of bupropion hydroxylation. A consideration of the effects of these variables on CYP2B6 mRNA and protein levels suggests that alcohol use is associated with enhanced CYP2B6 gene transcription, but the presence of a

ubc.ca

OBJECTIVE: There are limited data comparing medication strategies in patients with treatment-resistant depression. In this study, we compared the effects of combining citalopram and bupropion-SR versus switching to the other monotherapy in treatment-resistant depression. METHOD: This was a naturalistic, open-label cohort study. Patients with DSM-IV major depressive disorder who had not responded to at least 1 previous antidepressant and at least 6 weeks of treatment with citalopram or bupropion-SR were treated in a standard clinical protocol. In alternate months, eligible consecutive patients were treated by adding citalopram or bupropion-SR, or by switching to the other medication. Patients were assessed at baseline and after 6 weeks of treatment with the 29-item version of the Structured Interview Guide for the Hamilton Depression Rating Scale, Seasonal Affective Disorders Version (SIGH-SAD). RESULTS: A total of 61 patients completed the study: 32 in the combination condition and 29 in the monotherapy switch condition. The combination condition was superior to the monotherapy switch in the SIGH-SAD change score (-14.8 vs. -10.1, respectively, p <.04) and the proportion of patients in clinical remission (28% vs. 7%, p <.05). There were no differences in the proportion of patients who had side effects or in the severity of the side effects experienced. CONCLUSION: The results of this cohort study suggest that combining citalopram and bupropion-SR is more effective than switching to a monotherapy. Combination treatment was well tolerated with no greater side effect burden than monotherapy. Limitations of this study include the nonrandomized design,

ulleval.no

The sustained-release (SR) form of bupropion is an effective treatment for smokers who are trying to give up. As it is a prescription drug, the use of bupropion SR has brought smoking cessation back to the physician's office. Another unique feature of the use of bupropion SR for smoking cessation is that it is started before the smoker quits. Few head-to-head trials have compared bupropion SR with other medical treatments. However, trials have been conducted in a wide range of patient and treatment settings. These include community volunteers, patients with chronic obstructive pulmonary disease and cardiovascular disease, relapsed smokers, individuals with a history of depression, women and the elderly. Beyond randomised clinical trials, the effectiveness of bupropion has been shown in clinical practice and managed-care settings.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15102559&dopt=Abstract Bupropion Wellbutrin




Int J Clin Pract. 2004 Mar;58(3):285-91.
Bupropion as an aid to smoking cessation: a review of real-life effectiveness.

Holmes S, Zwar N, Jimenez-Ruiz CA, Ryan PJ, Browning D, Bergmann L, Johnston JA.

Fairfield Hospital, Fairfield, NSW, Australia.

Clinical trials rigorously demonstrate the efficacy of new products and justify their marketing. However, it is only after use in real-life settings that the clinical value (effectiveness) of a new treatment is fully known. The purpose of this review was to summarise the effectiveness data for bupropion SR as an aid to smoking cessation. Available reports of effectiveness data for bupropion SR were obtained from the literature, presentations at smoking cessation meetings and from the manufacturer. Twelve sources of effectiveness data were found and included clinical practice trials, observational studies/surveys, motivational support programme results and employer-based cessation programme results. The 6-month point prevalence smoking cessation rates ranged from 25 to 49%. There is a growing body of evidence supporting the effectiveness of bupropion SR as an aid to smoking cessation. Real-life quit rates for bupropion SR are similar to those seen in the original clinical trial programme.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15117097&dopt=Abstract Bupropion Wellbutrin