Rosuvastatin and Losartan Pharmacokinetics After Bariatric Surgery

Anatomical and physiological changes after bariatric surgery may alter oral drug absorption, first-pass metabolism, transporter activity, and systemic exposure. RYGB bypasses the duodenum and proximal jejunum, whereas sleeve gastrectomy preserves intestinal continuity but reduces gastric volume and may accelerate gastric emptying. Rosuvastatin is strongly influenced by transporters such as OATP1B1 and BCRP; losartan is affected by absorption and CYP2C9-mediated formation of its active metabolite E-3174. Direct comparative evidence between these procedures is limited. Eligible adults will be enrolled before clinically indicated surgery. Surgical procedure selection is not assigned by the study. At each pharmacokinetic visit, after at least 8 hours of fasting, participants will receive single oral doses of rosuvastatin 10 mg and losartan 25 mg with 200 mL water. Venous plasma samples will be obtained at 0, 1.5, and 4 hours. Concentrations of rosuvastatin, losartan, and E-3174 will be quantified using validated HPLC-MS/MS. Individual AUC0-infinity, apparent clearance, half-life, and apparent volume of distribution will be estimated using MAP Bayesian methods informed by published population pharmacokinetic models. Clinical and laboratory covariates, including weight, BMI, lipid profile, blood pressure, comorbidities, and concomitant medications, will be recorded. In the 30-participant RYGB group only, paired stool samples will be analyzed by 16S rRNA sequencing and untargeted metabolomics. Safety will be monitored during and after each research dosing visit.