AAPS PharmSciTech. 2003;4(1):E3.
Studies in formulation and pharmacotechnical evaluation of controlled release transdermal delivery system of bupropion.

Gondaliya D, Pundarikakshudu K.

Shree S. K. Patel College of Pharmaceutical Education and Research, Ganpat Vidyanagar, Kherva - 382711, District Mehsana, Gujarat, India.

The objective of the present study was to design and evaluate unilaminate transdermal adhesive matrix systems capable of diffusing bupropion base at a constant rate over an extended period of time as an alternative route of administration. Unilaminate transdermal adhesive matrices have been fabricated with different concentrations of Eudragit E as the adhesive and rate-controlling polymer. The in vitro release and epidermal flux through human cadaver skin were studied. The release of drug from the matrices obeyed zero order release kinetics (r2 = 0.9810 to 0.9960). The delivery rate of bupropion ranged from 10.5 mg to 31.4 mg per day from a 3.14 cm2 area of matrix. The relation between concentration of bupropion base in matrix and epidermal flux, concentration of drug in matrix, and epidermal adsorption of bupropion during diffusion follow hyperbolic fashion. Triethylcitrate (TEC) and dibutylphthalate (DBP) have no influence on the diffusion of bupropion through human cadaver skin when used as plasticizers. Incorporation of succinic acid in the adhesive matrix retarded diffusion due to the formation of rigid cross linking of the polymer, while propylene glycol and myristic acid, alone or in combination, significantly enhanced the flux of bupropion through human cadaver skin.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12916913&dopt=Abstract Bupropion Wellbutrin

lareb.nl

AIMS: To investigate the cause of chest pain during the use of bupropion as an aid to stop smoking. METHODS: The Netherlands Pharmacovigilance Centre received 22 reports of chest pain, associated with the use of bupropion 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. 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, but its origin remains unclear.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12968991&dopt=Abstract Bupropion Wellbutrin




J Pharm Biomed Anal. 2003 Sep 19;33(2):287-93.
HPLC determination and pharmacokinetics of sustained-release bupropion tablets in dogs.

Zhang D, Yuan B, Qiao M, Li F.

Department of Analytical Chemistry, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.

The pharmacokinetics and bioequivalency of a newly developed sustained-release bupropion tablet was studied in six dogs after single oral administration and compared with a regular tablet (RT) in randomized two-period crossover design. A sensitive and rapid HPLC method was developed and validated for the quantitative determination of bupropion in dog plasma. The compound and the internal standard (I.S.) (hydroxyethylfludiazepam) were extracted from the plasma samples by liquid-liquid extraction. The extracts were analyzed by a reversed-phase HPLC with 50 mmol/l phosphate buffer (pH 5.5)-methanol (45:55, v/v) as the eluent. The assay was specific for bupropion. The calibration curves were linear in the range between 1 and 750 ng/ml. The validated lower limit of quantification was 1 ng/ml. The overall precision (expressed as R.S.D.) of quality controls were within 15%. The method was successfully applied to the bioequivalency study of bupropion in the two formulations. The Cmax of sustained-release tablet (ST) was significantly lower than that of the RT and the Tmax was significantly longer than that of the RT (P<0.05). The relative bioavailability of the ST was (99.1+/-1.51)%, the results of ANOVA and two one sided tests indicated that the new ST exhibited good sustained release properties and was bioequivalent to the RT.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12972093&dopt=Abstract Bupropion Wellbutrin

charite.de

Bupropion is applied in depression and smoking cessation. Genetic polymorphisms in cytochrome P450 2B6 (CYP2B6) may cause variability in bupropion pharmacokinetics since hydroxylation is known to be mediated by CYP2B6. Bupropion may be a probe drug for CYP2B6 activity in humans. Bupropion pharmacokinetics were studied after a single oral dose of 150 mg in 121 healthy male volunteers. The amino acid polymorphisms R22C, Q172H, S259R, K262R and R487C were analysed by polymerase chain reaction and restriction fragment length polymorphism and plasma concentrations were measured by high-performance liquid chromatography. Pharmacokinetic analysis was performed by non-parametric methods and by population pharmacokinetic modelling. A unimodal distribution of bupropion and hydroxybupropion kinetic parameters was detected with a mean (range) area under the curve (AUC) of 3.64 (0.89-8.14) micromol.h/l for bupropion and 25.5 (6.72-75.3) micromol.h/l for hydroxybupropion. Population kinetic analysis revealed that bupropion total clearance via CYP2B6 alleles *1, *2, *5 and *6 did not differ, but clearance via allele *4 was 1.66-fold higher compared to wild-type allele *1 (P=0.001). Corresponding to the high clearance of bupropion, carriers of the CYP2B6 genotype *1/*4 had significantly higher Cmax of hydroxybupropion compared to all other genotypes (P=0.03). Only a minor fraction of the variability in bupropion and hydroxybupropion kinetics could be explained by the known CYP2B6 amino acid variants, in particular by the CYP2B6*4 allele. The role of this allele should also be studied in other CYP2B6 substrates, including cyclophosphamide, halothane,




Biol Psychiatry. 2003 Oct 15;54(8):800-5.
In vivo activity of bupropion at the human dopamine transporter as measured by positron emission tomography.

Learned-Coughlin SM, Bergstrom M, Savitcheva I, Ascher J, Schmith VD, Langstrom B.

GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709, USA.

BACKGROUND: Converging lines of evidence are consistent with an inhibitory effect of the antidepressant and smoking-cessation aid bupropion on dopamine and norepinephrine reuptake, but the in vivo effects of the drug at the human dopamine transporter (DAT) have not been studied to date. This study employed positron emission tomography (PET) to assess the extent and duration of DAT receptor occupancy by bupropion and its metabolites under conditions of steady-state oral dosing with bupropion sustained-release (SR) in healthy volunteers. METHODS: Six healthy male volunteers received bupropion SR 150 mg daily on days 1 through 3 and 150 mg every 12 hours on day 4 through the morning of day 11. PET investigations were performed between 1 and 7 days before initiation of bupropion SR dosing, as well as 3, 12, and 24 hours after the last dose of bupropion SR on day 11. RESULTS: Bupropion and its metabolites inhibited striatal uptake of the selective DAT-binding radioligand (11)C-betaCIT-FE in vivo. Three hours after the last dose of bupropion SR, average DAT occupancy by bupropion and its metabolites was 26%-a level that was maintained through the last PET assessment at 24 hours after dosing. CONCLUSIONS: Bupropion and its metabolites induced a low occupancy of the striatal DAT over 24 hours under conditions of steady-state oral dosing with therapeutic doses of bupropion SR. These data are consistent with the hypothesis that dopamine reuptake inhibition may be responsible in part for the therapeutic effects of the drug.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14550679&dopt=Abstract Bupropion Wellbutrin