Bupropion: pharmacological and clinical profile in smoking cessation

Ko, Haustein

doi:10.5414/cpp41056

Cited by 28 publications

(20 citation statements)

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“…Interestingly, rifampin coadministration resulted in a shorter hydroxybupropion half‐life and a significant reduction in the AUC 0–∞ of this metabolite. This observation is consistent with rifampin also influencing the elimination of hydroxybupropion; however, detailed information on the routes of elimination of hydroxybupropion has not been reported in the literature 30 . Reduced concentrations of threohydrobupropion and erythrohydrobupropion were also observed after rifampin administration and are consistent with decreased substrate availability, resulting from the lower systemic concentrations attained as a consequence of the increased apparent clearance of bupropion.…”

Section: Discussionsupporting

confidence: 79%

Cytochrome P450 2B6 activity as measured by bupropion hydroxylation: Effect of induction by rifampin and ethnicity

Loboz¹,

Gross²,

Williams³

et al. 2006

Clinical Pharmacology & Therapeutics

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Rifampin significantly induces CYP2B6 activity in vivo, and the clinical consequences of potential interactions between rifampin and CYP2B6 substrates deserve further investigation. Rifampin appears to induce the elimination of hydroxybupropion. Differences in bupropion pharmacokinetics that were observed between white subjects and Chinese subjects can be attributed to differences in body weight, suggesting that, for a given subject weight, CYP2B6 activity is similar in white subjects and Chinese subjects.

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Section: Discussionsupporting

confidence: 79%

Cytochrome P450 2B6 activity as measured by bupropion hydroxylation: Effect of induction by rifampin and ethnicity

Loboz¹,

Gross²,

Williams³

et al. 2006

Clinical Pharmacology & Therapeutics

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“…5,6 Bupropion, which was developed originally as an antidepressant, is now approved as non-nicotine pharmacotherapy for smoking cessation. 21,35 A unique feature of bupropion for smoking cessation is that it can be started before the target quit date. [36][37][38] Smoking cessation using the combination of nicotine patches and bupropion has a higher success rate than that using placebo.…”

Section: Discussionmentioning

confidence: 99%

Chronic effect of nicotine on serotonin transporter mRNA in the raphe nucleus of rats: Reversal by co‐administration of bupropion

Semba

Wakuta

2008

Psychiatry Clin Neurosci

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Aim: Epidemiologic studies suggest the existence of a biological link between nicotine withdrawal and depression. To investigate the neuronal mechanisms of the precipitation of depression during smoking cessation, an animal model of nicotine withdrawal was used, and the expression of serotonin transporter (5HTT), abnormality of which is implicated in the pathogenesis of depression, was investigated. The effect of co-administration of bupropion, which has been clinically shown to ameliorate nicotine withdrawal symptoms, was also investigated in this model. Methods:Male Wistar rats were implanted with a minipump s.c., which delivered nicotine at a rate of 6 mg/kg per day for 12 days (days 1-12). Rats given chronic nicotine were killed on day 13, or 2 days after the removal of minipump (withdrawal day 2). In a separate experiment, bupropion (15 or 30 mg/kg per day) was injected into the nicotine infused rats on days 2-12. The expression of mRNA for 5HTT in the dorsal raphe was determined on in situ hybridization.Results: Chronic nicotine infusion resulted in the reduction of 5HTT mRNA expression, which lasted through withdrawal day 2. Co-administration of bupropion, however, significantly antagonized this reduction.Conclusions: Chronic nicotine infusion reduces the synthesis of 5HTT protein, which may consequently precipitate depression during nicotine withdrawal, but co-administration of bupropion may ameliorate withdrawal symptoms by counteracting nicotine's effect on 5HTT.

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“…1 It has one chiral center, which is used clinically as a racemic mixture 2 and its enantiomers have been shown to undergo rapid racemisation in solution. 3 Bupropion is metabolized to three active metabolites: hydroxybupropion, erythrohydrobupropion, and threohydrobupropion ( Fig.…”

Section: Bupropion (Amfebutamone) (Rac)-2-tert-butylamino-3mentioning

confidence: 99%

Stereoselective analysis of hydroxybupropion and application to drug interaction studies

Loboz

Gross

et al. 2006

Chirality

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A sensitive and stereoselective assay has been developed for the quantitation of the enantiomers of hydroxybupropion, an active metabolite of bupropion, in human plasma. The assay used liquid-liquid extraction and a Cyclobond I 2000 HPLC column with a mobile phase containing 3% acetonitrile, 0.5% triethylamine, and 20 mM ammonium acetate (pH 3.8). The technique was linear over the concentration range of 12.5-500 ng/ml for (2R,3R)- and (2S,3S)-hydroxybupropion. The method was reproducible as both interday and intraday variabilities were less than 10% for both hydroxybupropion enantiomers. Overall extraction recovery of hydroxybupropion enantiomers and the internal standard phenacetin from plasma was greater than 80% and reproducible over the concentration range of 12.5-500 ng/ml for each enantiomer. The limit of quantification (LOQ) of hydroxybupropion enantiomers was 12.5 ng/ml. The stereoselective pharmacokinetics of both (2R,3R)- and (2S,3S)-hydroxybupropion in healthy male subjects (n = 16) were investigated after a single dose of (rac)-bupropion either alone or during rifampicin administration. (2R,3R)-Hydroxybupropion was the predominant enantiomer present in plasma. A stereoselective effect of rifampicin on hydroxybupropion concentrations was observed, with rifampicin influencing the pharmacokinetics of each hydroxybupropion enantiomer in a different manner. The ratio of (2R,3R)-hydroxybupropion (AUC(0-24)) to (2S,3S)-hydroxybupropion (AUC(0-24)) increased from 4.9 +/- 1.6 to 8.3 +/- 1.9 during rifampicin administration (P < 0.001). A time-dependent change in the hydroxybupropion enantiomeric ratio was observed after (rac)-bupropion administration both before and during rifampicin coadministration, with an increase in the relative proportion of (2S,3S)-hydroxybupropion over the 24 h postdose period.

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Bupropion: pharmacological and clinical profile in smoking cessation

Cited by 28 publications

References 0 publications

Cytochrome P450 2B6 activity as measured by bupropion hydroxylation: Effect of induction by rifampin and ethnicity

Cytochrome P450 2B6 activity as measured by bupropion hydroxylation: Effect of induction by rifampin and ethnicity

Chronic effect of nicotine on serotonin transporter mRNA in the raphe nucleus of rats: Reversal by co‐administration of bupropion

Stereoselective analysis of hydroxybupropion and application to drug interaction studies

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