About this trial

This prospective, open-label, non-randomized pharmacokinetic study will evaluate how Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy affect systemic exposure to single oral test doses of rosuvastatin and losartan. Sixty adults scheduled for bariatric surgery will enter one of two parallel groups according to the clinically selected operation (30 RYGB and 30 sleeve gastrectomy). Each participant will receive rosuvastatin 10 mg and losartan 25 mg once within 30 days before surgery and again approximately 12 weeks after surgery. Plasma samples collected before dosing and at 1.5 and 4 hours after dosing will be used with maximum a posteriori Bayesian estimation to estimate individual pharmacokinetic parameters. In the 30-participant RYGB group only, paired stool samples will be used to explore gut microbiota and untargeted fecal metabolomic changes. The primary objective is to compare within-participant changes and between-procedure differences in drug exposure after bariatric surgery.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Adults aged 18 to 65 years;

Formal clinical indication for RYGB or sleeve gastrectomy after multidisciplinary assessment;

Bariatric surgery scheduled and no previous bariatric procedure;

Able to understand the study and provide written informed consent.

Disqualifiers

Moderate or severe hepatic impairment, liver enzymes greater than 3 times the upper limit of normal, or Child-Pugh class B or C.

Estimated glomerular filtration rate below 30 mL/min/1.73 m².

Concomitant use of drugs that substantially affect rosuvastatin pharmacokinetics and cannot be temporarily discontinued, including cyclosporine, gemfibrozil, or potent OATP1B1/BCRP or CYP2C9 inhibitors.

Systemic antibiotic use within 3 months or probiotic, prebiotic, or synbiotic use within 4 weeks before sampling.

Trial design

Design model

Parallel

Treatments tested in this trial

Rosuvastatin
Drug
Rosuvastatin 10 mg tablet, single oral dose at each of two pharmacokinetic visits. Other name: rosuvastatin calcium.
Losartan (Control)
Drug
Losartan 25 mg tablet, single oral dose at each of two pharmacokinetic visits. Other name: losartan potassium.

Treatment groups

60 Participants

are divided into 2 treatment groups

Group A: Roux-en-Y Gastric Bypass GroupExperimental treatment 2 interventions

Group B: Sleeve Gastrectomy GroupActive comparator 2 interventions

Trial outcomes

Primary outcomes

1

Change in rosuvastatin area under the plasma concentration-time curve extrapolated to infinity (AUC0-infinity)

Individual rosuvastatin AUC0-infinity will be estimated from plasma concentrations at 0, 1.5, and 4 hours using maximum a posteriori Bayesian estimation based on a published population pharmacokinetic model. Within-participant postoperative/preoperative geometric mean ratios and between-procedure differences will be estimated.

Time frame

Within 30 days before surgery and approximately 12 weeks after surgery (postoperative visit may be delayed up to 6 months for clinical safety).

2

Change in losartan area under the plasma concentration-time curve extrapolated to infinity (AUC0-infinity)

Individual losartan AUC0-infinity will be estimated using the same sparse-sampling MAP Bayesian strategy and a published parent-metabolite population model.

Time frame