Pharmacokinetic and pharmacodynamic of bupropion: integrative overview of relevant clinical and forensic aspects.

Abstract:

:Bupropion is an atypical antidepressant of the aminoketone group, structurally related to cathinone, associated with a wide interindividual variability. An extensive pharmacokinetic and pharmacodynamic review of bupropion was performed, also focusing on chemical, pharmacological, toxicological, clinical and forensic aspects of this drug without a limiting period. Bupropion is a chiral, basic, highly lipophilic drug, clinically used as racemate that undergoes extensive stereoselective metabolism. Its major active metabolites, hydroxybupropion, threohydrobupropion, and erythrohydrobupropion reach higher plasma concentrations than bupropion. Bupropion exerts its effects mainly by inhibiting dopamine and norepinephrine reuptake and by blocking several nicotinic receptors. Recent reports highlight recreational use of bupropion via intranasal insufflation and intravenous use. Seizures, insomnia, agitation, headache, dry mouth, and nausea are some of the reported adverse effects. Neurologic effects are major signs of intoxication that should be carefully managed. Finally, the characterization of the polymorphic enzymes involved in the metabolism of bupropion is essential to understand factors that may influence the interindividual and intraindividual variability in bupropion metabolite exposure, including the evaluation of potential drug-drug interactions and pharmacogenetic implications.

journal_name

Drug Metab Rev

journal_title

Drug metabolism reviews

authors

Costa R,Oliveira NG,Dinis-Oliveira RJ

doi

10.1080/03602532.2019.1620763

subject

Has Abstract

pub_date

2019-08-01 00:00:00

pages

293-313

issue

3

eissn

0360-2532

issn

1097-9883

journal_volume

51

pub_type

杂志文章,评审
  • The pharmacokinetics of glycyrrhizic acid evaluated by physiologically based pharmacokinetic modeling.

    abstract::Glycyrrhizic acid is widely applied as a sweetener in food products and chewing tobacco. In addition, it is of clinical interest for possible treatment of chronic hepatitis C. In some highly exposed subjects, side effects such as hypertension and symptoms associated with electrolyte disturbances have been reported. To...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.1081/dmr-100104400

    authors: Ploeger B,Mensinga T,Sips A,Seinen W,Meulenbelt J,DeJongh J

    更新日期:2001-05-01 00:00:00

  • Quinone reductases multitasking in the metabolic world.

    abstract::The multiple functions of NAD(P)H:quinone oxidoreductase 1 (NQO1, DT-diaphorase) in the cell are reviewed. NQO1 has long been viewed as a chemoprotective enzyme involved in cellular defense against the electrophilic and oxidizing metabolites of xenobiotic quinones. It also participates in reduction of endogenous quino...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.1081/dmr-200033465

    authors: Ross D

    更新日期:2004-10-01 00:00:00

  • Disposition of a series of tetrahydrocarbazoles.

    abstract::Cyclindole was extensively metabolized and eliminated primarily via the kidneys from most laboratory animals and man. Only in the dog was cyclindole a major urinary component. Cyclindole was metabolized by N-demethylation and/or hydroxylation. In studies utilizing radiolabeled drug, the primary urinary component was p...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.3109/03602538008994027

    authors: Edelson J,Benziger DP

    更新日期:1980-01-01 00:00:00

  • Pharmacogenetic screening of the gene deletion and duplications of CYP2D6.

    abstract::Cytochrome P450 (CYP) 2D6 is one of the most important enzymes involved in the metabolism of drugs. Multiple, clinically relevant, genetic variants of this gene have been identified and, among them, a gene deletion as well as multiplications of the gene. These large structural mutations in CYP2D6 occur at a relatively...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.1080/03602530600952206

    authors: Meijerman I,Sanderson LM,Smits PH,Beijnen JH,Schellens JH

    更新日期:2007-01-01 00:00:00

  • Ros-induced histone modifications and their role in cell survival and cell death.

    abstract::Much is known about the distal DNA damage repair response. In particular, many of the enzymes and auxiliary proteins that participate in DNA repair have been characterized. In addition, knowledge of signaling pathways activated in response to DNA damage is increasing. In contrast, comparatively less is known of DNA da...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.1080/03602530600959649

    authors: Monks TJ,Xie R,Tikoo K,Lau SS

    更新日期:2006-01-01 00:00:00

  • Ronald Estabrook's early guidance of a postdoctoral fellow concerning the intricacies of steroid metabolism by cytochromes P450.

    abstract::Ronald Estabrook made his initial impact studying cytochrome P450 by demonstrating the oxidative metabolism function of this unique class of enzymes, which had an unusual spectral peak at 450 nm when reduced and in the presence of carbon monoxide. Utilizing a photochemical action spectrum, he demonstrated that a cytoc...

    journal_title:Drug metabolism reviews

    pub_type: 传,历史文章,杂志文章

    doi:10.1080/03602530701468318

    authors: Sheets JJ

    更新日期:2007-01-01 00:00:00

  • Covalent binding of xenobiotics to specific proteins in the liver.

    abstract::Chemicals that cause toxicity though a direct mechanism, such as acetaminophen, covalently bind to a select group of proteins prior to the development of toxicity, and these proteins may be important in the initiation of the events that lead to the hepatotoxicity. Disruption of the cell is measured by release of intra...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.3109/03602539709037572

    authors: Pumford NR,Halmes NC,Hinson JA

    更新日期:1997-02-01 00:00:00

  • The right compound in the right assay at the right time: an integrated discovery DMPK strategy.

    abstract::The high rate of attrition during drug development and its associated high research and development (R&D) cost have put pressure on pharmaceutical companies to ensure that candidate drugs going to clinical testing have the appropriate quality such that the biological hypothesis could be evaluated. To help achieve this...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.3109/03602532.2012.691099

    authors: Ballard P,Brassil P,Bui KH,Dolgos H,Petersson C,Tunek A,Webborn PJ

    更新日期:2012-08-01 00:00:00

  • Entering the era of computationally driven drug development.

    abstract::Historically, failure rates in drug development are high; increased sophistication and investment throughout the process has shifted the reasons for attrition, but the overall success rates have remained stubbornly and consistently low. Only 8% of new entities entering clinical testing gain regulatory approval, indica...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.1080/03602532.2020.1726944

    authors: Maharao N,Antontsev V,Wright M,Varshney J

    更新日期:2020-05-01 00:00:00

  • PharmGKB: understanding the effects of individual genetic variants.

    abstract::The Pharmacogenetics and Pharmacogenomics Knowledge Base (PharmGKB: http://www.pharmgkb.org) is devoted to disseminating primary data and knowledge in pharmacogenetics and pharmacogenomics. We are annotating the genes that are most important for drug response and present this information in the form of Very Important ...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章

    doi:10.1080/03602530802413338

    authors: Sangkuhl K,Berlin DS,Altman RB,Klein TE

    更新日期:2008-01-01 00:00:00

  • Contamination of the air with mineral fibers following the explosive destruction of buildings and fire.

    abstract::Mineral fibers, including asbestos, are ubiquitous contaminants of the environment. Asbestos fibers are generally present at levels below 1 fiber/L in air though 10 fibers/L may be found in cities; these levels do not appear to be high enough to present a hazard to health. These fibers come mostly from the use of fibr...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.3109/03602539408998321

    authors: Hoskins JA,Brown RC

    更新日期:1994-01-01 00:00:00

  • N-hydroxyarylamines.

    abstract::Aryl and heterocyclic amines are of particular interest because of their carcinogenicity. The N-hydroxy derivatives are formed by oxidation, usually by the cytochrome P450 (P450) enzymes and most often by P450 family 1. The mechanism of oxidation appears to resemble that of other P450 reactions. The N-hydroxy products...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.1081/dmr-120005663

    authors: Guengerich FP

    更新日期:2002-08-01 00:00:00

  • Mechanisms regulating human FMO3 transcription.

    abstract::Flavin-containing monooxygenases (FMOs) are important oxidative drug metabolizing enzymes. FMO3 is the primary human adult liver FMO enzyme, but is developmentally regulated. FMO3 promoter characterization using in vitro DNA binding assays with HepG2 cell and fetal and adult liver nuclear protein, as well as FMO3/repo...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章

    doi:10.1080/03602530701498612

    authors: Klick DE,Hines RN

    更新日期:2007-01-01 00:00:00

  • Drugs as CYP3A probes, inducers, and inhibitors.

    abstract::Human cytochrome P450 (CYP) 3A subfamily members (mainly CYP3A4 and CYP3A5) mediate the metabolism of approximately half all marketed drugs and thus play a critical role in the drug metabolism. A huge number of studies on CYP3A-mediated drug metabolism in humans have demonstrated that CYP3A activity exhibits marked et...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.1080/03602530701690374

    authors: Liu YT,Hao HP,Liu CX,Wang GJ,Xie HG

    更新日期:2007-01-01 00:00:00

  • The biological actions of dehydroepiandrosterone involves multiple receptors.

    abstract::Dehydroepiandrosterone has been thought to have physiological functions other than as an androgen precursor. The previous studies performed have demonstrated a number of biological effects in rodents, such as amelioration of disease in diabetic, chemical carcinogenesis, and obesity models. To date, activation of the p...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.1080/03602530600569877

    authors: Webb SJ,Geoghegan TE,Prough RA,Michael Miller KK

    更新日期:2006-01-01 00:00:00

  • S-carboxymethyl-L-cysteine.

    abstract::S-carboxymethyl-L-cysteine, the side-chain carboxymethyl derivative of the sulfur-containing amino acid, cysteine, has been known and available for almost 80 years. During this time, it has been put to a variety of uses, but it is within the field of respiratory medicine that, presently, it has found a clinical niche....

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.3109/03602532.2011.631015

    authors: Mitchell SC,Steventon GB

    更新日期:2012-05-01 00:00:00

  • Structure and regulation of P-450s in the rat P450IIA gene subfamily.

    abstract::The rat P450IIA subfamily was characterized at the protein, cDNA, and gene level. The purified IIA1 and IIA2 P-450s displayed distinct positional specificities toward hydroxylation of the prototype substrate testosterone. The IIA1 and IIA2 genes were also regulated differently during development; IIA1 was expressed wi...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章

    doi:10.3109/03602538909103582

    authors: Gonzalez FJ,Matsunaga T,Nagata K

    更新日期:1989-01-01 00:00:00

  • A comprehensive insight of novel antioxidant therapies for atrial fibrillation management.

    abstract::Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and is associated with decreased quality of life, and increased mortality and morbidity from stroke and thromboembolism. The underlying mechanisms involved in the development of AF have yet to be fully elucidated. However, once initiated, AF t...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.3109/03602532.2015.1077858

    authors: Orenes-Piñero E,Valdés M,Lip GY,Marín F

    更新日期:2015-08-01 00:00:00

  • Allosteric modulators of cannabinoid receptor 1: developing compounds for improved specificity.

    abstract::The cannabinoid receptor 1 (CB1) is a G protein-coupled receptor (GPCR) that is located primarily in the central nervous system. CB1 is a therapeutic target which may impact pathways to mediate pain, neurodegenerative disorders, hunger, and drug-seeking behavior. Despite these benefits, development of orthosteric ther...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.1080/03602532.2018.1428342

    authors: Dopart R,Lu D,Lichtman AH,Kendall DA

    更新日期:2018-02-01 00:00:00

  • On the mechanism of hepatocarcinogenesis of benzodiazepines: evidence that diazepam and oxazepam are CYP2B inducers in rats, and both CYP2B and CYP4A inducers in mice.

    abstract::The aim of this study was to evaluate diazepam and oxazepam as cytochrome P450 inducers at doses previously shown to cause liver tumors in mice but not rats. In rats, diazepam and oxazepam induced CYP2B, and were as effective as phenobarbital despite lacking phenobarbital's tumor-promoting effect in rats. In mice, dia...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章

    doi:10.1080/03602530600570081

    authors: Parkinson A,Leonard N,Draper A,Ogilvie BW

    更新日期:2006-01-01 00:00:00

  • Metabolism of bioconjugate therapeutics: why, when, and how?

    abstract::Bioconjugation of therapeutic agents has been used as a selective drug delivery platform for many therapeutic areas. Bioconjugates are prepared by the covalent linkage of active compounds (small or large molecule) to a carrier molecule (lipids, proteins, peptides, carbohydrates, and polymers) through a chemical linker...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.1080/03602532.2020.1716784

    authors: Liu H,Bolleddula J,Nichols A,Tang L,Zhao Z,Prakash C

    更新日期:2020-02-01 00:00:00

  • Function and regulation of multidrug resistance proteins (MRPs) in the renal elimination of organic anions.

    abstract::The reabsorptive and excretory capacity of the kidney has an important influence on the systemic concentration of drugs. Multidrug resistance proteins (MRP/ABCC) expressed in the kidney play a critical role in the tubular efflux of a wide variety of drugs and toxicants, and, in particular, of their negatively charged ...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.1080/03602530500205275

    authors: van de Water FM,Masereeuw R,Russel FG

    更新日期:2005-01-01 00:00:00

  • Predictive models for human glucose-6-phosphate dehydrogenase deficiency.

    abstract::The present paper has discussed available test systems for determination of the response of G-6-PD-deficient human erythrocytes to environmental agents. The limitations and advantages of each model have been examined, and the results of research using each model have been presented. The future development of suitable ...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.3109/03602538608998292

    authors: Horton HM,Calabrese EJ

    更新日期:1986-01-01 00:00:00

  • Molecular and environmental causes of cancer.

    abstract::The multistep, clonal evolution model of cancer predicts fundamental mechanisms by which chemicals may influence the cancer process. These are illustrated by studies of the mechanisms of induction of carcinogenesis by estrogens and the inhibition of carcinogenesis by caloric restriction. ...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.1081/dmr-100100567

    authors: Barrett JC

    更新日期:2000-05-01 00:00:00

  • Practical aspects of transporter model systems: a case study involving SQV.

    abstract::In this case study, in vitro and in vivo data were provided for saquinavir (SQV) showing that drug transporters play a significant role in the absorption and disposition of drugs. This article is focused on the more practical points with a technical emphasis. Currently many in vitro and in vivo experimental models hav...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.1081/dmr-120037570

    authors: Su Y,Lee SH,Sinko PJ

    更新日期:2004-05-01 00:00:00

  • The role of positron emission tomography in pharmacokinetic analysis.

    abstract::The physiological and biochemical measurements that can be performed noninvasively in humans with modern imaging techniques offer great promise for defining the precise state of a patient's disease and its response to therapy. In general, there are two critical points in drug development when PET measurements are like...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.3109/03602539709002238

    authors: Fischman AJ,Alpert NM,Babich JW,Rubin RH

    更新日期:1997-11-01 00:00:00

  • Sulfotransferase genes: regulation by nuclear receptors in response to xeno/endo-biotics.

    abstract::Pregnane X receptor (PXR) and constitutive active/androstane receptor (CAR), members of the nuclear receptor superfamily, are two major xeno-sensing transcription factors. They can be activated by a broad range of lipophilic xenobiotics including therapeutics drugs. In addition to xenobiotics, endogenous compounds suc...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.3109/03602532.2013.835630

    authors: Kodama S,Negishi M

    更新日期:2013-11-01 00:00:00

  • The role of hepatic and extrahepatic UDP-glucuronosyltransferases in human drug metabolism.

    abstract::At present, the methods and enzymology of the UDP-glucuronosyltransferases (UGTs) lag behind that of the cytochromes P450 (CYPs). About 15 human UGTs have been identified, and knowledge about their regulation, substrate selectivity, and tissue distribution has progressed recently. Alamethicin has been characterized as...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.1081/dmr-120000653

    authors: Fisher MB,Paine MF,Strelevitz TJ,Wrighton SA

    更新日期:2001-08-01 00:00:00

  • Drug-induced hyperbilirubinemia and the clinical influencing factors.

    abstract::Hyperbilirubinemia may accompany harmful effects such as jaundice, brain dysfunction, and pharmacokinetic alterations of drugs. Clinical drugs are the important causes of hyperbilirubinemia, especially for patients with certain pathologic conditions or with genetic variations. This article reviews hyperbilirubinemic p...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.1080/03602530802341133

    authors: Ah YM,Kim YM,Kim MJ,Choi YH,Park KH,Son IJ,Kim SG

    更新日期:2008-01-01 00:00:00

  • Novel pathways associated with quinone-induced stress in breast cancer cells.

    abstract::Hormone-dependent breast cancers that overexpress the ligand-binding nuclear transcription factor, estrogen receptor (ER), represent the most common form of breast epithelial malignancy. Exposure of breast epithelial cells to a redox-cycling and arylating quinone induces mitogen-activated protein kinase phosphorylatio...

    journal_title:Drug metabolism reviews

    pub_type: 杂志文章,评审

    doi:10.1080/03602530600959391

    authors: Benz CC,Atsriku C,Yau C,Britton D,Schilling B,Gibson BW,Baldwin MA,Scott GK

    更新日期:2006-01-01 00:00:00