Vis enkel innførsel

dc.contributor.authorKrogstad, Veronica
dc.contributor.authorPeric, Alexandra
dc.contributor.authorRobertsen, Ida
dc.contributor.authorKringen, Marianne K.
dc.contributor.authorVistnes, Maria
dc.contributor.authorHjelmesæth, Jøran
dc.contributor.authorSandbu, Rune
dc.contributor.authorJohnson, Line Kristin
dc.contributor.authorAngeles, Philip Carlo Soriano
dc.contributor.authorJansson-Löfmark, Rasmus
dc.contributor.authorKarlsson, Cecilia
dc.contributor.authorAndersson, Shalini
dc.contributor.authorÅsberg, Anders
dc.contributor.authorAndersson, Tommy B.
dc.contributor.authorChristensen, Hege Staaland
dc.date.accessioned2020-11-15T15:39:49Z
dc.date.accessioned2021-02-11T08:27:01Z
dc.date.available2020-11-15T15:39:49Z
dc.date.available2021-02-11T08:27:01Z
dc.date.issued2020-10-18
dc.identifier.citationKrogstad V, Peric A, Robertsen I, Kringen MKK, Vistnes MV, Hjelmesæth J, Sandbu R, Johnson LK, Angeles PC, Jansson-Löfmark R, Karlsson C, Andersson S, Åsberg A, Andersson TB, Christensen HS. Correlation of body weight and composition with hepatic activities of cytochrome P450 enzymes . Journal of Pharmaceutical Sciences. 2020en
dc.identifier.issn0022-3549
dc.identifier.issn1520-6017
dc.identifier.urihttps://hdl.handle.net/10642/9515
dc.description.abstractObesity is associated with comorbidities of which pharmacological treatment is needed. Physiological changes associated with obesity may influence the pharmacokinetics of drugs, but the effect of body weight on drug metabolism capacity remains uncertain. The aim of this study was to investigate ex vivo activities of hepatic drug metabolizing CYP enzymes in patients covering a wide range of body weight. Liver biopsies from 36 individuals with a body mass index (BMI) ranging from 18 to 63 kg/m2 were obtained. Individual hepatic microsomes were prepared and activities of CYP3A, CYP2B6, CYP2C8, CYP2D6, CYP2C9, CYP2C19 and CYP1A2 were determined. The unbound intrinsic clearance (CLint,u) values for CYP3A correlated negatively with body weight (r = −0.43, p < 0.01), waist circumference (r = −0.47, p < 0.01), hip circumference (r = −0.51, p < 0.01), fat percent (r = −0.41, p < 0.05), fat mass (r = −0.48, p < 0.01) and BMI (r = −0.46, p < 0.01). Linear regression analysis showed that CLint,u values for CYP3A decreased with 5% with each 10% increase in body weight (r2 = 0.12, β = −0.558, p < 0.05). There were no correlations between body weight measures and CLint,u values for the other CYP enzymes investigated. These results indicate reduced hepatic metabolizing capacity of CYP3A substrates in patients with increasing body weight.en
dc.language.isoenen
dc.publisherWileyen
dc.relation.ispartofseriesJournal of Pharmaceutical Sciences;Volume 110, Issue 1
dc.rightsCreative Commons Attribution 4.0 International (CC BY 4.0) Licenseen
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectCytochrome P450en
dc.subjectDrug metabolizing enzymesen
dc.subjectFirst pass metabolismsen
dc.subjectHepatic metabolismsen
dc.subjectHuman liver microsomesen
dc.subjectPhase 1 metabolismsen
dc.titleCorrelation of body weight and composition with hepatic activities of cytochrome P450 enzymesen
dc.typeJournal article
dc.typePeer revieweden
dc.date.updated2020-11-15T15:39:49Z
dc.description.versionpublishedVersionen
dc.identifier.doihttps://doi.org/10.1016/j.xphs.2020.10.027
dc.identifier.cristin1842517
dc.source.journalJournal of Pharmaceutical Sciences


Tilhørende fil(er)

Thumbnail

Denne innførselen finnes i følgende samling(er)

Vis enkel innførsel

Creative Commons Attribution 4.0 International (CC BY 4.0) License
Med mindre annet er angitt, så er denne innførselen lisensiert som Creative Commons Attribution 4.0 International (CC BY 4.0) License