Use of Enantiomeric Bupropion and Hydroxybupropion to Assess CYP2B6 Activity in Glomerular Kidney Diseases

Joy, Melanie S.; Frye, Reginald F.; Stubbert, Kristi; Brouwer, Kim L. R.; Falk, Ronald J.; Kharasch, Evan D.

doi:10.1177/0091270009353031

Cited by 15 publications

(16 citation statements)

References 34 publications

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“…In performing these assessments, we investigated the clinical pharmacokinetics of flurbiprofen, a pharmacologic probe of CYP2C9 metabolism; fexofenadine, a nonspecific probe of drug transport; and erythromycin, a probe of CYP3A4 metabolism in vivo. Previous results by our group indicated reductions in CYP2B6 activity (assessed by bupropion) in patients with glomerulonephritis compared with other subject groups . A secondary objective of the study was to compare the activity of CYP3A4 and CYP2C9 and drug transport in glomerulonephritis compared with nonglomerular CKD and with previous published reports in healthy controls and in patients with ESRD.…”

mentioning

confidence: 90%

“…Previous results by our group indicated reductions in CYP2B6 activity (assessed by bupropion) in patients with glomerulonephritis compared with other subject groups. 16 A secondary objective of the study was to compare the activity of CYP3A4 and CYP2C9 and drug transport in glomerulonephritis compared with nonglomerular CKD and with previous published reports in healthy controls and in patients with ESRD.…”

Section: O R I G I N a L R E S E A R C H A R T I C L E Smentioning

confidence: 99%

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In Vivo Alterations in Drug Metabolism and Transport Pathways in Patients with Chronic Kidney Diseases

et al. 2013

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Study Objective-This study was designed to prospectively evaluate the in vivo activities of drug transporters, metabolizing enzymes and pharmacokinetics in patients with chronic kidney diseases (CKD) caused by glomerulonephritis and non-glomerular etiologies. Design-A prospective study design Participants-Eighteen adults with CKD Setting-General Clinical Research Center at the University of North Carolina and University of PittsburghMeasurement and Main Results-Blood and urine were collected and assayed for fexofenadine (transporter function) as well as flurbiprofen and 4-hydroxyflurbiprofen (CYP2C9 function). CYP3A4 activity was assessed by the erythromycin breath test. In patients with glomerulonephritis, the apparent oral clearance of fexofenadine (representing transporter activity) was 58.8±34.4L/h, documenting a 40% reduction compared with previous data in healthy controls. The CYP2C9 pathway (4-hydroxyflurbiprofen formation clearance), was similar in all the patients with CKD and was concordant with previous reports of patients with end-stage renal disease (ESRD) and healthy controls. For flurbiprofen, patients with glomerulonephritis had higher oral clearance than those with nonglomeruler CKD, suggesting higher unbound fraction and enhanced metabolism through other (non-CYP2C9) routes. No statistically significant differences in CYP3A4 activity were observed in either group of patients, or when compared with results from previous studies of patients with ESRD or healthy controls. Conclusions-The current study suggests no statistically significant differences in the in vivo activity of CYP2C9 and CYP3A4 in patients with either glomerulonephritis or non-glomerular CKD. However, there are clinical differences in transporter function as defined by at least a 25% reduction in activity in glomerulonephritis as opposed to healthy controls. A similarity in the in vivo function between patients with glomerulonephritis and ESRD, and between patients with glomerulonephritis and non-glomerular CKD was present despite significant differences in kidney function. Further in vivo and in vitro studies are necessary to fully understand the physiologic and disease-specific nuances that contribute to alterations in drug disposition in patients with kidney diseases.

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confidence: 90%

Section: O R I G I N a L R E S E A R C H A R T I C L E Smentioning

confidence: 99%

In Vivo Alterations in Drug Metabolism and Transport Pathways in Patients with Chronic Kidney Diseases

et al. 2013

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“…Similarly Joy et al . () used LC‐MS for quantification of R ‐ and S ‐bupropion and ( R , R )‐ and ( S , S )‐hydroxybupropion of plasma and urine samples. SPE was used in extraction of R ‐ and S ‐bupropion and ( R , R )‐ and ( S , S )‐hydroxybupropion from plasma and urine.…”

Section: Stereo‐specific Lc and Lc‐ms Bioassaysmentioning

confidence: 99%

Stereo‐specific LC and LC‐MS bioassays of antidepressants and psychotics

Rao

Prasad

2014

Biomedical Chromatography

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Stereochemistry in drug action is gaining importance because the enantiomers often differ in their biological activity and pharmacokinetic profiles. The use of racemic drugs may contribute to adverse effects owing to the presence of either inactive or toxic enantiomers. Most of the drugs currently used to treat psychiatric disorders, including depression, contain one or more chiral centers and are mostly sold as racemates. Single-enantiomer drugs provide greater selectivity for their biological targets, improved therapeutic indices and better pharmacokinetics compared with racemates. Therefore it is of great importance to monitor body fluid/tissue levels of drugs used to treat depression and psychiatric disorders. The present manuscript gives an overview of liquid chromatographic and mass spectrometric techniques reported during 2000-2013 for enantiomeric separation of various classes of antidepressants, viz. selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, noradrenergic and specific serotonergic antidepressants, norepinephrine reuptake inhibitors, norepinephrine-dopamine reuptake inhibitors, nonamphetamine central nervous system stimulants, serotonin and dopamine inhibitors and γ-aminobutyric acid receptor agonists in biological matrices. Techniques used for extraction, separation and quantification are discussed.

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“…Phenethylamine (PEA), the simplest endogenous aromatic amine and potential pharmacophore, provides the basic chemical structure for several classes of drugs with wide biological activity. [1][2][3][4] Owing to this reason, PEA derivatives have attracted intensive interests recently and a series of new ones has been obtained from natural organisms and chemical syntheses, which exhibited diverse bioactivities, including bronchiectasia, antidepressant, stimulant, etc. 5,6 Nowadays, they have emerged as a promising biologically active scaffold in the search of new agents against human diseases.…”

Section: Introductionmentioning

confidence: 99%

“…In our ongoing work to search for antimicrobial components from marine microorganisms, five new PEA derivatives (1)(2)(3)(4)(5) were isolated from the strain of Arenibacter nanhaiticus sp. nov. NH36A T derived from the marine sediment of the South China Sea.…”

Section: Introductionmentioning

confidence: 99%

New phenethylamine derivatives from Arenibacter nanhaiticus sp. nov. NH36AT and their antimicrobial activity

Chen

Tang

et al. 2013

J Antibiot

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Five new phenethylamine (PEA) derivatives (1-5) were isolated from the strain of Arenibacter nanhaiticus sp. nov. NH36A(T) derived from the marine sediment of the South China Sea by bioassay-guided fractionation. Their structures were elucidated by spectroscopic methods including UV, IR, HR-MS and NMR. Interestingly, compounds 1-4 existed as enantiomers, which were resolved by chiral liquid chromatography. The resolved configuration of each enantiomer was assigned by the Marfey's method. Of these compounds, 5 showed weak antimicrobial activity against Staphylococcus aureus and Bacillus subtilis with MIC values of 0.50 and 0.25 mg ml(-1), respectively.

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Use of Enantiomeric Bupropion and Hydroxybupropion to Assess CYP2B6 Activity in Glomerular Kidney Diseases

Cited by 15 publications

References 34 publications

In Vivo Alterations in Drug Metabolism and Transport Pathways in Patients with Chronic Kidney Diseases

In Vivo Alterations in Drug Metabolism and Transport Pathways in Patients with Chronic Kidney Diseases

Stereo‐specific LC and LC‐MS bioassays of antidepressants and psychotics

New phenethylamine derivatives from Arenibacter nanhaiticus sp. nov. NH36AT and their antimicrobial activity

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