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Open Access 29-03-2023 | Pharmacokinetics | Original Research Article

Neither Gastric Bypass Surgery Nor Diet-Induced Weight-Loss Affect OATP1B1 Activity as Measured by Rosuvastatin Oral Clearance

Authors: Markus Hovd, Ida Robertsen, Line Kristin Johnson, Veronica Krogstad, Christine Wegler, Kine Eide Kvitne, Marianne Kristiansen Kringen, Eva Skovlund, Cecilia Karlsson, Shalini Andersson, Per Artursson, Rune Sandbu, Jøran Hjelmesæth, Anders Åsberg, Rasmus Jansson-Löfmark, Hege Christensen

Published in: Clinical Pharmacokinetics | Issue 5/2023

Abstract

Introduction

Rosuvastatin 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.

Methods

Patients 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).

Results

A 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.

Conclusions

Neither 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.

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Title: Neither Gastric Bypass Surgery Nor Diet-Induced Weight-Loss Affect OATP1B1 Activity as Measured by Rosuvastatin Oral Clearance
Authors: Markus Hovd
Ida Robertsen
Line Kristin Johnson
Veronica Krogstad
Christine Wegler
Kine Eide Kvitne
Marianne Kristiansen Kringen
Eva Skovlund
Cecilia Karlsson
Shalini Andersson
Per Artursson
Rune Sandbu
Jøran Hjelmesæth
Anders Åsberg
Rasmus Jansson-Löfmark
Hege Christensen
Publication date: 29-03-2023
Publisher: Springer International Publishing
Keywords: Pharmacokinetics
Rosuvastatin
Published in: Clinical Pharmacokinetics / Issue 5/2023
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI: https://doi.org/10.1007/s40262-023-01235-5

Keynote webinar | Spotlight on medication adherence

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Neither Gastric Bypass Surgery Nor Diet-Induced Weight-Loss Affect OATP1B1 Activity as Measured by Rosuvastatin Oral Clearance

Abstract

Introduction

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusions

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