Linked Life Data

18287571

Source:http://linkedlifedata.com/resource/pubmed/id/18287571

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-3-18
pubmed:abstractText
The clearance of racemic bupropion, metabolized selectively by CYP2B6 in vitro, has been used clinically to phenotype CYP2B6 activity, polymorphisms, and drug interactions but has known limitations. Bupropion hydroxylation by CYP2B6 is stereoselective. This investigation assessed the stereoselectivity of bupropion pharmacokinetics and the influence of CYP2B6 induction. Ten healthy volunteers received immediate-release bupropion before and after 7 days of rifampin. Plasma and urine bupropion and hydroxybupropion were analyzed using a stereoselective assay. Plasma area under the curve (AUC(0-infinity)) and maximum concentrations were 3-fold greater for R- than S-bupropion. Bupropion apparent oral clearance was 3- and 2-fold greater for S- than R- and R,S-bupropion, respectively. Hydroxybupropion plasma AUC(0-infinity) and elimination half-life were significantly less for (S,S)- than (R,R)- and the racemate. (S,S)-hydroxybupropion was formation rate limited, whereas (R,R)-hydroxybupropion and the racemate were elimination rate limited. Rifampin doubled both R- and S-bupropion clearance and caused 4-fold increases in both (R,R)- and (S,S)-hydroxybupropion formation clearances. Increases in the plasma hydroxybupropion/bupropion AUC(0-infinity) ratio were greater for (S,S)- than (R,R)-hydroxybupropion. Simplified plasma and urine metrics of stereoselective bupropion metabolism and clearance were identified. Because metabolite formation clearance is the best in vivo metric of enzyme activity and due, therefore, to faster S-bupropion elimination and formation rate-limited (S,S)-hydroxybupropion kinetics, stereoselective S-bupropion hydroxylation and (S,S)-hydroxybupropion formation clearance may be a useful and improved phenotypic probe for CYP2B6.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0091-2700
pubmed:author
pubmed:issnType
Print
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
464-74
pubmed:meshHeading
pubmed-meshheading:18287571-Adult, pubmed-meshheading:18287571-Aged, pubmed-meshheading:18287571-Aged, 80 and over, pubmed-meshheading:18287571-Antidepressive Agents, Second-Generation, pubmed-meshheading:18287571-Area Under Curve, pubmed-meshheading:18287571-Aryl Hydrocarbon Hydroxylases, pubmed-meshheading:18287571-Bupropion, pubmed-meshheading:18287571-Cross-Over Studies, pubmed-meshheading:18287571-Drug Interactions, pubmed-meshheading:18287571-Female, pubmed-meshheading:18287571-Genotype, pubmed-meshheading:18287571-Half-Life, pubmed-meshheading:18287571-Humans, pubmed-meshheading:18287571-Hydroxylation, pubmed-meshheading:18287571-Male, pubmed-meshheading:18287571-Middle Aged, pubmed-meshheading:18287571-Oxidoreductases, N-Demethylating, pubmed-meshheading:18287571-Phenotype, pubmed-meshheading:18287571-Rifampin, pubmed-meshheading:18287571-Stereoisomerism
pubmed:year
2008
pubmed:articleTitle
Stereoselective bupropion hydroxylation as an in vivo phenotypic probe for cytochrome P4502B6 (CYP2B6) activity.
pubmed:affiliation
Division of Clinical and Translational Research, Department of Anesthesiology, Washington University, St. Louis, MO 63110-1093, USA. kharasch@wustl.edu
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural