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Neither Gastric Byp...
Neither Gastric Bypass Surgery Nor Diet-Induced Weight-Loss Affect OATP1B1 Activity as Measured by Rosuvastatin Oral Clearance
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- Hovd, M. (author)
- Univ Oslo, Dept Pharm, Sect Pharmacol & Pharmaceut Biosci, POB 0316, N-1068 Oslo, Norway.
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- Robertsen, I. (author)
- Univ Oslo, Dept Pharm, Sect Pharmacol & Pharmaceut Biosci, POB 0316, N-1068 Oslo, Norway.
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- Johnson, L. K. (author)
- Vestfold Hosp Trust, Morbid Obes Ctr, POB 2168, N-3103 Tonsberg, Norway.
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- Krogstad, V. (author)
- Univ Oslo, Dept Pharm, Sect Pharmacol & Pharmaceut Biosci, POB 0316, N-1068 Oslo, Norway.
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- Wegler, Christine (author)
- Uppsala universitet,Institutionen för farmaci,AstraZeneca, DMPK Res & Early Dev Cardiovasc Renal & Metab, BioPharmaceut R&D, Pepparedsleden 1, S-43183 Mölndal, Sweden.
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- Kvitne, K. E. (author)
- Univ Oslo, Dept Pharm, Sect Pharmacol & Pharmaceut Biosci, POB 0316, N-1068 Oslo, Norway.
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- Kringen, M. K. (author)
- Diakonhjemmet Hosp, Ctr Psychopharmacol, Oslo, Norway.;OsloMet Oslo Metropolitan Univ, Dept Hlth Sci, Oslo, Norway.
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- Skovlund, E. (author)
- Norwegian Univ Sci & Technol, Dept Publ Hlth & Nursing, POB 8905, N-7491 Trondheim, Norway.
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- Karlsson, Cecilia (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,AstraZeneca, Late Stage Dev, Cardiovasc Renal & Metab, BioPharmaceut R&D, Gothenburg, Sweden.;Univ Gothenburg, Inst Med, Sahlgrenska Acad, Dept Mol & Clin Med, Gothenburg, Sweden.
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- Andersson, S. (author)
- AstraZeneca, Oligonucleotide Discovery, Discovery Sci, BioPharmaceut R&D, Gothenburg, Sweden.
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- Artursson, Per (author)
- Uppsala universitet,Institutionen för farmaci,Science for Life Laboratory, SciLifeLab
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- Sandbu, R. (author)
- Vestfold Hosp Trust, Morbid Obes Ctr, POB 2168, N-3103 Tonsberg, Norway.;Vestfold Hosp Trust, Dept Surg, Tonsberg, Norway.
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- Hjelmesaeth, J. (author)
- Vestfold Hosp Trust, Morbid Obes Ctr, POB 2168, N-3103 Tonsberg, Norway.;Univ Oslo, Inst Clin Med, Dept Endocrinol Morbid Obes & Prevent Med, POB 1171, N-0318 Oslo, Norway.
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- Asberg, A. (author)
- Univ Oslo, Dept Pharm, Sect Pharmacol & Pharmaceut Biosci, POB 0316, N-1068 Oslo, Norway.;Oslo Univ Hosp, Dept Transplantat Med, POB 4950, N-0424 Oslo, Norway.
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- Jansson-Lofmark, R. (author)
- AstraZeneca, DMPK Res & Early Dev Cardiovasc Renal & Metab, BioPharmaceut R&D, Pepparedsleden 1, S-43183 Mölndal, Sweden.
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- Christensen, H. (author)
- Univ Oslo, Dept Pharm, Sect Pharmacol & Pharmaceut Biosci, POB 0316, N-1068 Oslo, Norway.
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Univ Oslo, Dept Pharm, Sect Pharmacol & Pharmaceut Biosci, POB 0316, N-1068 Oslo, Norway Vestfold Hosp Trust, Morbid Obes Ctr, POB 2168, N-3103 Tonsberg, Norway. (creator_code:org_t)
- 2023-03-29
- 2023
- English.
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In: Clinical Pharmacokinetics. - : Springer Science and Business Media LLC. - 0312-5963 .- 1179-1926. ; 62:5, s. 725-735
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Abstract
Subject headings
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- IntroductionRosuvastatin pharmacokinetics is mainly dependent on the activity of hepatic uptake transporter OATP1B1. In this study, we aimed to investigate and disentangle the effect of Roux-en-Y gastric bypass (RYGB) and weight loss on oral clearance (CL/F) of rosuvastatin as a measure of OATP1B1-activity.MethodsPatients with severe obesity preparing for RYGB (n = 40) or diet-induced weight loss (n = 40) were included and followed for 2 years, with four 24-hour pharmacokinetic investigations. Both groups underwent a 3-week low-energy diet (LED; < 1200 kcal/day), followed by RYGB or a 6-week very-low-energy diet (VLED; < 800 kcal/day).ResultsA total of 80 patients were included in the RYGB group (40 patients) and diet-group (40 patients). The weight loss was similar between the groups following LED and RYGB. The LED induced a similar (mean [95% CI]) decrease in CL/F in both intervention groups (RYGB: 16% [0, 31], diet: 23% [8, 38]), but neither induced VLED resulted in any further changes in CL/F. At Year 2, CL/F had increased by 21% from baseline in the RYGB group, while it was unaltered in the diet group. Patients expressing the reduced function SLCO1B1 variants (c.521TC/CC) showed similar changes in CL/F over time compared with patients expressing the wild-type variant.ConclusionsNeither body weight, weight loss nor RYGB per se seem to affect OATP1B1 activity to a clinically relevant degree. Overall, the observed changes in rosuvastatin pharmacokinetics were minor, and unlikely to be of clinical relevance.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kirurgi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Surgery (hsv//eng)
Keyword
- liver
- digestion
- efficacy
- 1b1
- Pharmacology & Pharmacy
Publication and Content Type
- ref (subject category)
- art (subject category)
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Hovd, M.
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Robertsen, I.
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Johnson, L. K.
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Krogstad, V.
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Wegler, Christin ...
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Kvitne, K. E.
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Kringen, M. K.
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Skovlund, E.
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Karlsson, Cecili ...
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Andersson, S.
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Artursson, Per
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Sandbu, R.
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Hjelmesaeth, J.
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Asberg, A.
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Jansson-Lofmark, ...
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Christensen, H.
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Pharmaceutical S ...
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Surgery
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Clinical Pharmac ...
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University of Gothenburg
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Uppsala University