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dc.contributor.authorKvitne, Kine Eide
dc.contributor.authorKrogstad, Veronica
dc.contributor.authorWegler, Christine
dc.contributor.authorJohnson, Line Kristin
dc.contributor.authorKringen, Marianne K.
dc.contributor.authorHovd, Markus Herberg
dc.contributor.authorHertel, Jens Kristoffer
dc.contributor.authorHeijer, Maria
dc.contributor.authorSandbu, Rune
dc.contributor.authorSkovlund, Eva
dc.contributor.authorArtursson, Per
dc.contributor.authorKarlsson, Cecilia
dc.contributor.authorAndersson, Shalini
dc.contributor.authorAndersson, Tommy B.
dc.contributor.authorHjelmesæth, Jøran Sture
dc.contributor.authorÅsberg, Anders
dc.contributor.authorJansson-Löfmark, Rasmus
dc.contributor.authorChristensen, Hege
dc.contributor.authorRobertsen, Ida
dc.date.accessioned2022-11-25T08:58:38Z
dc.date.available2022-11-25T08:58:38Z
dc.date.created2022-04-19T15:05:42Z
dc.date.issued2022
dc.identifier.issn0306-5251
dc.identifier.urihttps://hdl.handle.net/11250/3034032
dc.description.abstractAim Roux-en-Y gastric bypass (RYGB) may influence drug disposition due to surgery-induced gastrointestinal alterations and/or subsequent weight loss. The objective was to compare short- and long-term effects of RYGB and diet on the metabolic ratios of paraxanthine/caffeine (cytochrome P450 [CYP] 1A2 activity), 5-hydroxyomeprazole/omeprazole (CYP2C19 activity) and losartan/losartan carboxylic acid (CYP2C9 activity), and cross-sectionally compare these CYP-activities with normal-to-overweight controls. Methods This trial included patients with severe obesity preparing for RYGB (n = 40) or diet-induced (n = 41) weight loss, and controls (n = 18). Both weight loss groups underwent a 3-week low-energy diet (<1200 kcal/day, weeks 0-3) followed by a 6-week very-low-energy diet or RYGB (both <800 kcal/day, weeks 3-9). Follow-up time was 2 years, with four pharmacokinetic investigations. Results Mean ± SD weight loss from baseline was similar in the RYGB-group (13 ± 2.4%) and the diet group (10.5 ± 3.9%) at week 9, but differed at year 2 (RYGB −30 ± 6.9%, diet −3.1 ± 6.3%). From weeks 0 to 3, mean (95% confidence interval [CI]) CYP2C19 activity similarly increased in both groups (RYGB 43% [16, 55], diet 48% [22, 60]). Mean CYP2C19 activity increased by 30% (2.6, 43) after RYGB (weeks 3-9), but not in the diet-group (between-group difference −0.30 [−0.63, 0.03]). CYP2C19 activity remained elevated in the RYGB group at year 2. Baseline CYP2C19 activity was 2.7-fold higher in controls compared with patients with obesity, whereas no difference was observed in CYP1A2 and CYP2C9 activities. Conclusion Our findings suggest that CYP2C19 activity is lower in patients with obesity and increases following weight loss. This may be clinically relevant for drug dosing. No clinically significant effect on CYP1A2 and CYP2C9 activities was observed.en_US
dc.language.isoengen_US
dc.publisherBritish Pharmacological Societyen_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/deed.no*
dc.titleShort- and long-term effects of body weight, calorie restriction and gastric bypass on CYP1A2, CYP2C19 and CYP2C9 activityen_US
dc.title.alternativeShort- and long-term effects of body weight, calorie restriction and gastric bypass on CYP1A2, CYP2C19 and CYP2C9 activityen_US
dc.typePeer revieweden_US
dc.typeJournal articleen_US
dc.description.versionpublishedVersionen_US
dc.source.journalBritish Journal of Clinical Pharmacologyen_US
dc.identifier.doi10.1111/bcp.15349
dc.identifier.cristin2017639
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode2


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Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal
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