Longitudinal Impacts of Gastric Bypass Surgery on Pharmacodynamics and Pharmacokinetics of Statins

Purpose: Undergoing Roux-en-Y gastric bypass (RYGB) is expected to affect orally administered drug absorption. Statins are commonly prescribed to patients with obesity for the prevention of atherosclerotic cardiovascular diseases by lowering cholesterol. This is the first longitudinal prospective study on impacts of RYGB on weight loss, pharmacodynamics, and pharmacokinetics of atorvastatin, rosuvastatin, and simvastatin, and their active metabolites, up to 1-year post-surgery. Methods: Forty-six patients were recruited, five patients on atorvastatin, twelve on rosuvastatin, nine on simvastatin, and twenty on no statin. The concentrations of atorvastatin, rosuvastatin, and simvastatin with their active metabolites were monitored. Results: Mean plasma concentrations of atorvastatin and metabolites and rosuvastatin normalized by the unit dose [(nM)/(mg/kg)] decreased by 3- to 6-month post-surgery. Conversely, simvastatin and its metabolite concentrations increased up to 6-month post-surgery, then declined to preoperative levels by 1-year post-surgery. The metabolisms of atorvastatin to hydroxyl-metabolites and simvastatin to simvastatin acid were decreased after RYGB. The weight loss and PD outcomes were comparable between statin and non-statin groups suggesting the key impacts were from RYGB. The discontinuation or reduction of dose of atorvastatin or rosuvastatin post-RYGB exhibited rebounds of LDL levels in some subjects, but the rebound was not apparent with patients on simvastatin pre-surgery. Conclusion: Discontinuations of statin dosing post-RYGB require LDL monitoring and reducing the dose to half seems to have better results. Patients on statin treatment post-RYGB should be followed-up closely based on our pharmacokinetic findings, to ensure therapeutic effects of the treatment with minimal adverse effects