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Short- and long-ter...
Short- and long-term effects of body weight loss following calorie restriction and gastric bypass on CYP3A-activity - a non-randomized three-armed controlled trial
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- Kvitne, K. E. (författare)
- Univ Oslo, Sect Pharmacol & Pharmaceut Biosci, Dept Pharm, Oslo, Norway.
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- Robertsen, I. (författare)
- Univ Oslo, Sect Pharmacol & Pharmaceut Biosci, Dept Pharm, Oslo, Norway.
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- Skovlund, E. (författare)
- Norwegian Univ Sci & Technol, Dept Publ Hlth & Nursing, NTNU, Trondheim, Norway.
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- Christensen, H. (författare)
- Univ Oslo, Sect Pharmacol & Pharmaceut Biosci, Dept Pharm, Oslo, Norway.;Uppsala Univ, Dept Pharm, Uppsala, Sweden.;AstraZeneca, BioPharmaceut R&D, Res & Early Dev, Cardiovasc Renal & Metab,DMPK, Mölndal, Sweden.
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- Krogstad, V. (författare)
- Univ Oslo, Sect Pharmacol & Pharmaceut Biosci, Dept Pharm, Oslo, Norway.
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- Wegler, Christine (författare)
- Uppsala universitet,Institutionen för farmaci,AstraZeneca
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- Angeles, P. C. (författare)
- Vestfold Hosp Trust, Morbid Obes Ctr, Tonsberg, Norway.;Vestfold Hosp Trust, Dept Surg, Tonsberg, Norway.
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- Wollmann, B. M. (författare)
- Diakonhjemmet Hosp, Ctr Psychopharmacol, Oslo, Norway.
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- Hole, K. (författare)
- Diakonhjemmet Hosp, Ctr Psychopharmacol, Oslo, Norway.
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- Johnson, L. K. (författare)
- Vestfold Hosp Trust, Morbid Obes Ctr, Tonsberg, Norway.
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- Sandbu, R. (författare)
- Vestfold Hosp Trust, Morbid Obes Ctr, Tonsberg, Norway.;Vestfold Hosp Trust, Dept Surg, Tonsberg, Norway.
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- Artursson, Per (författare)
- Uppsala universitet,Institutionen för farmaci,Science for Life Laboratory, SciLifeLab
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- Karlsson, Cecilia, 1968 (författare)
- Gothenburg 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, Latestage Dev Cardiovasc Renal & Metab, Mölndal, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.
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- Andersson, S. (författare)
- AstraZeneca, BioPharmaceut R&D, Res & Early Dev, Discovery Sci, Mölndal, Sweden.
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- Andersson, T. B. (författare)
- AstraZeneca, BioPharmaceut R&D, Res & Early Dev, Cardiovasc Renal & Metab,DMPK, Mölndal, Sweden.
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- Hjelmesaeth, J. (författare)
- Vestfold Hosp Trust, Morbid Obes Ctr, Tonsberg, Norway.;Univ Oslo, Inst Clin Med, Dept Endocrinol Morbid Obes & Prevent Med, Oslo, Norway.
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- Jansson-Lofmark, R. (författare)
- AstraZeneca, BioPharmaceut R&D, Res & Early Dev, Cardiovasc Renal & Metab,DMPK, Mölndal, Sweden.
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- Asberg, A. (författare)
- Univ Oslo, Sect Pharmacol & Pharmaceut Biosci, Dept Pharm, Oslo, Norway.;Oslo Univ Hosp, Dept Transplantat Med, POB 4950, N-0424 Oslo, Norway.
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Univ Oslo, Sect Pharmacol & Pharmaceut Biosci, Dept Pharm, Oslo, Norway Norwegian Univ Sci & Technol, Dept Publ Hlth & Nursing, NTNU, Trondheim, Norway. (creator_code:org_t)
- 2021-08-26
- 2022
- Engelska.
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Ingår i: Cts-Clinical and Translational Science. - : Wiley. - 1752-8054 .- 1752-8062. ; 15:1, s. 221-233
- Relaterad länk:
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https://www.duo.uio....
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- It remains uncertain whether pharmacokinetic changes following Roux-en-Y gastric bypass (RYGB) can be attributed to surgery-induced gastrointestinal alterations per se and/or the subsequent weight loss. The aim was to compare short- and long-term effects of RYGB and calorie restriction on CYP3A-activity, and cross-sectionally compare CYP3A-activity with normal weight to overweight controls using midazolam as probe drug. This three-armed controlled trial included patients with severe obesity preparing for RYGB (n = 41) 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) followed by a 6-week very-low-energy-diet or RYGB (both <800 kcal/day). Patients were followed for 2 years, with four pharmacokinetic investigations using semisimultaneous oral and intravenous dosing to determine changes in midazolam absolute bioavailability and clearance, within and between groups. The RYGB and diet groups showed similar weight-loss at week 9 (13 +/- 2.4% vs. 11 +/- 3.6%), but differed substantially after 2 years (-30 +/- 7.0% vs. -3.1 +/- 6.3%). At baseline, mean absolute bioavailability and clearance of midazolam were similar in the RYGB and diet groups, but higher compared with controls. On average, absolute bioavailability was unaltered at week 9, but decreased by 40 +/- 7.5% in the RYGB group and 32 +/- 6.1% in the diet group at year 2 compared with baseline, with no between-group difference. No difference in clearance was observed over time, nor between groups. In conclusion, neither RYGB per se nor weight loss impacted absolute bioavailability or clearance of midazolam short term. Long term, absolute bioavailability was similarly decreased in both groups despite different weight loss, suggesting that the recovered CYP3A-activity is not only dependent on weight-loss through RYGB.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kirurgi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Surgery (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- morbidly obese-patients
- bariatric surgery
- pharmacokinetic model
- systemic exposure
- cyp3a activity
- midazolam
- metabolism
- liver
- 4-beta-hydroxycholesterol
- bioavailability
- Research & Experimental Medicine
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
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Kvitne, K. E.
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Robertsen, I.
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Skovlund, E.
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Christensen, H.
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Krogstad, V.
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Wegler, Christin ...
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visa fler...
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Angeles, P. C.
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Wollmann, B. M.
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Hole, K.
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Johnson, L. K.
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Sandbu, R.
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Artursson, Per
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Karlsson, Cecili ...
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Andersson, S.
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Andersson, T. B.
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Hjelmesaeth, J.
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Jansson-Lofmark, ...
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Asberg, A.
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Kirurgi
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Farmaceutiska ve ...
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Cts-Clinical and ...
- Av lärosätet
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Göteborgs universitet
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Uppsala universitet