Rosuvastatin and Losartan Pharmacokinetics After Bariatric Surgery

NCT07748273 | Not Yet Recruiting

• 2 other identifiers: HCFMRP-PK-BARI-2026CAAE 98218026.5.0000.5440
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Bariatric Surgery; Drug Absorption; Obesity & Overweight; Pharmacokinetics After Oral Intake

Keywords

Roux-en-Y gastric bypass; sleeve gastrectomy; rosuvastatin; losartan; E-3174; gut microbiota; metabolomics; systemic exposure

Outcome Measures

Primary Outcomes (2)

• 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.

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

• 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.

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

Secondary Outcomes (11)

• Change in apparent oral clearance (CL/F) of rosuvastatin, losartan, and E-3174; same two study visits.

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

• Change in estimated elimination half-life of rosuvastatin, losartan, and E-3174; same two study visits.

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

• Change in plasma concentrations of rosuvastatin, losartan, and E-3174 at 1.5 and 4 hours after the single oral dose; each pharmacokinetic visit.

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

• Incidence of adverse events following research test dosing, assessed from dose administration through completion of the 4-hour observation period at each visit and by clinically indicated follow-up.

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

• In the RYGB group only (30 participants), change in gut microbial in paired stool samples

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

Study Arms (2)

Roux-en-Y Gastric Bypass Group

EXPERIMENTAL

Participants scheduled for clinically indicated laparoscopic RYGB receive a single oral research dose of rosuvastatin 10 mg plus losartan 25 mg within 30 days before surgery and again approximately 12 weeks after surgery. Plasma is collected at 0, 1.5, and 4 hours at each visit. Paired stool samples are collected before and after surgery for microbiome and untargeted metabolomics analyses.

Drug: Rosuvastatin; Drug: Losartan (Control)

Sleeve Gastrectomy Group

ACTIVE COMPARATOR

Participants scheduled for clinically indicated laparoscopic sleeve gastrectomy receive the same single oral research doses and pharmacokinetic plasma sampling schedule before and approximately 12 weeks after surgery. Stool collection and microbiome/metabolomics analyses are not performed in this group.

Drug: Rosuvastatin; Drug: Losartan (Control)

Interventions

Rosuvastatin DRUG

Rosuvastatin 10 mg tablet, single oral dose at each of two pharmacokinetic visits. Other name: rosuvastatin calcium.

Roux-en-Y Gastric Bypass Group; Sleeve Gastrectomy Group

Losartan (Control) DRUG

Losartan 25 mg tablet, single oral dose at each of two pharmacokinetic visits. Other name: losartan potassium.

Roux-en-Y Gastric Bypass Group; Sleeve Gastrectomy Group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Continuous current rosuvastatin or other statin therapy unless medically discontinued with an adequate washout period under physician supervision.
• Clinically relevant baseline hypotension, significant hyperkalemia, renal impairment, or another condition that makes a losartan test dose unsafe.
• Severe postoperative complication preventing oral dosing, including active gastrointestinal leak, intractable vomiting, or severe anastomotic stenosis.
• Pregnancy. Participants of childbearing potential undergo routine preoperative beta-hCG testing.

Sponsors & Collaborators

• Hospital das Clínicas de Ribeirão Preto: lead
• School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo: collaborator

Study Sites (1)

Hospital das Clínicas, Ribeirão Preto Medical School, University of São Paulo

Ribeirão Preto, São Paulo, 14048900, Brazil

Location

MeSH Terms

Conditions

Obesity; Overweight

Interventions

Rosuvastatin Calcium; Losartan

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Imidazoles; Azoles; Tetrazoles

Study Officials

• Wilson Salgado Jr, MD PhD

  Medical School of Ribeirao Preto, University of Sao Paulo

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wilson Salgado Jr, MD, PhD

CONTACT

+5516981564846; wsalgado@fmrp.usp.br

Joao A Ferreira-Filho, MD

CONTACT

+5516988250557; joaoalmiroff@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants enter the RYGB or sleeve gastrectomy group according to the operation selected for clinical care. Within each group, every participant undergoes identical paired pharmacokinetic test-dose visits before and after surgery.

Study Record Dates

• First Submitted: July 22, 2026
• First Posted: August 5, 2026
• Study Start: August 2, 2026
• Primary Completion (Estimated): May 15, 2027
• Study Completion (Estimated): May 15, 2027
• Last Updated: August 5, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Beginning 6 months after publication of the main results and available for 5 years.
• Access Criteria: Qualified researchers with a methodologically sound proposal approved by the principal investigator and relevant institutional authorities. Requests: wsalgado@fmrp.usp.br.

Locations

BR (1)