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  • Kvitne, K. E.Univ Oslo, Dept Pharm, Sect Pharmacol & Pharmaceut Biosci, PO 1068 Blindern, N-0316 Oslo, Norway. (author)

Short- and long-term effects of body weight, calorie restriction and gastric bypass on CYP1A2, CYP2C19 and CYP2C9 activity

  • Article/chapterEnglish2022

Publisher, publication year, extent ...

  • 2022-04-25
  • Wiley,2022

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/319048
  • https://gup.ub.gu.se/publication/319048URI
  • https://doi.org/10.1111/bcp.15349DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-495117URI

Supplementary language notes

  • Language:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Aim 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.

Subject headings and genre

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  • Krogstad, V.Univ Oslo, Dept Pharm, Sect Pharmacol & Pharmaceut Biosci, PO 1068 Blindern, N-0316 Oslo, Norway. (author)
  • Wegler, ChristineUppsala universitet,Institutionen för farmaci,AstraZeneca, BioPharmaceut R&D, Cardiovasc Renal & Metab, DMPK,Res & Early Dev, Mölndal, Sweden(Swepub:uu)chrwe731 (author)
  • Johnson, L. K.Vestfold Hosp Trust, Morbid Obes Ctr, Tonsberg, Norway. (author)
  • Kringen, M. K.Diakonhjemmet Hosp, Ctr Psychopharmacol, Oslo, Norway.;Oslo Metropolitan Univ, Dept Hlth Sci, Oslo, Norway. (author)
  • Hovd, M. H.Univ Oslo, Dept Pharm, Sect Pharmacol & Pharmaceut Biosci, PO 1068 Blindern, N-0316 Oslo, Norway.,AstraZeneca, BioPharmaceut R&D, Clin Pharmacol & Safety Sci, Clin Pharmacol & Quantitat Pharmacol, Mölndal, Sweden. (author)
  • Hertel, J. K.Vestfold Hosp Trust, Morbid Obes Ctr, Tonsberg, Norway. (author)
  • Heijer, M. (author)
  • Sandbu, R.Vestfold Hosp Trust, Morbid Obes Ctr, Tonsberg, Norway.;Vestfold Hosp Trust, Dept Surg, Tonsberg, Norway. (author)
  • Skovlund, E.Norwegian Univ Sci & Technol, Dept Publ Hlth & Nursing, NTNU, Trondheim, Norway. (author)
  • Artursson, PerUppsala universitet,Institutionen för farmaci,Science for Life Laboratory, SciLifeLab(Swepub:uu)perartur (author)
  • Karlsson, Cecilia,1968Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,AstraZeneca, BioPharmaceut R&D, Late Stage Dev, Cardiovasc Renal & Metab, Mölndal, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden. (author)
  • Andersson, S.AstraZeneca, BioPharmaceut R&D, Discovery Sci, Res & Early Dev, Mölndal, Sweden. (author)
  • Andersson, T. B.AstraZeneca, BioPharmaceut R&D, Cardiovasc Renal & Metab, DMPK,Res & Early Dev, Mölndal, Sweden. (author)
  • Hjelmesaeth, J.Vestfold Hosp Trust, Morbid Obes Ctr, Tonsberg, Norway.;Univ Oslo, Inst Clin Med, Dept Endocrinol Morbid Obes & Prevent Med, Oslo, Norway. (author)
  • Asberg, A.Univ Oslo, Dept Pharm, Sect Pharmacol & Pharmaceut Biosci, PO 1068 Blindern, N-0316 Oslo, Norway.;Oslo Univ Hosp, Dept Transplantat Med, Oslo, Norway. (author)
  • Jansson-Lofmark, R.AstraZeneca, BioPharmaceut R&D, Cardiovasc Renal & Metab, DMPK,Res & Early Dev, Mölndal, Sweden. (author)
  • Christensen, H.Univ Oslo, Dept Pharm, Sect Pharmacol & Pharmaceut Biosci, PO 1068 Blindern, N-0316 Oslo, Norway. (author)
  • Robertsen, I.Univ Oslo, Dept Pharm, Sect Pharmacol & Pharmaceut Biosci, PO 1068 Blindern, N-0316 Oslo, Norway. (author)
  • Univ Oslo, Dept Pharm, Sect Pharmacol & Pharmaceut Biosci, PO 1068 Blindern, N-0316 Oslo, Norway.Institutionen för farmaci (creator_code:org_t)

Related titles

  • In:British Journal of Clinical Pharmacology: Wiley88:9, s. 4121-41330306-52511365-2125

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