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

• Published in: Clinical pharmacokinetics 2023-05, Vol.62 (5), p.725-735
• Main Authors: Hovd, Markus, Robertsen, Ida, Johnson, Line Kristin, Krogstad, Veronica, Wegler, Christine, Kvitne, Kine Eide, Kringen, Marianne Kristiansen, Skovlund, Eva, Karlsson, Cecilia, Andersson, Shalini, Artursson, Per, Sandbu, Rune, Hjelmesæth, Jøran, Åsberg, Anders, Jansson-Löfmark, Rasmus, Christensen, Hege
• Format: Article
• Language: English
• Subjects: 1b1; Biopsy; Body mass index; Cholecystectomy; Comorbidity; Diet; digestion; Drug dosages; efficacy; Enzymes; Farmakologi och toxikologi; Gastric Bypass - methods; Gastrointestinal surgery; Hospitals; Humans; Internal Medicine; Investigations; Laboratories; liver; Liver-Specific Organic Anion Transporter 1 - genetics; Medicine; Medicine & Public Health; Obesity; Obesity, Morbid; Original; Original Research Article; Overweight; Pharmacokinetics; Pharmacology & Pharmacy; Pharmacology and Toxicology; Pharmacology/Toxicology; Pharmacotherapy; Plasma; Polypeptides; Proteins; Rosuvastatin Calcium; Tumor necrosis factor-TNF; Weight control; Weight Loss
• ISSN: 0312-5963; 1179-1926; 1179-1926
• DOI: 10.1007/s40262-023-01235-5

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.