Impact of Bariatric Surgery on Pharmacokinetic Study of Simvastatin and Carvedilol

Summary

Obesity affects more than 1 in 3 adults in the U.S. It is commonly associated with reduced quality of life and complications such as metabolic syndrome, heart disease, high blood pressure and sleep disorders. The gastric bypass, also known as Roux-en-Y gastric bypass (RYGB), is one of the most common weight-loss surgeries due to the reliable and long-lasting weight loss and the effective remission of obesity-associated conditions. Although the impact of obesity on absorption, distribution, metabolism and excretion has been documented for several drugs, label recommendations might not account for specific population subgroups, specially morbidly obese patients and obese patients post-bariatric surgery. This study aims to investigate the impact of obesity and RYGB surgery on the kinetic disposition of simvastatin (Study A) and carvedilol (Study B).

Conditions

• Obesity
• Bariatric Surgery
• Roux-en Y Gastric Bypass

Interventions

PROCEDURE

Digestive biopsy

All patients with indication for RYGB bariatric surgery undergo to endoscopy before and after the surgery as standard protocol. Digestive biopsy are being performed in obese and post-RYGB patients for transcriptomic analysis

DRUG

Carvedilol 25mg

Single-dose of carvedilol 25 mg are being administrated orally.

PROCEDURE

Serial blood sampling for PK analysis

Serial blood samples are being collected at times 0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18 and 24 hours after drug administration for PK evaluation .

DRUG

Metoprolol 100 mg for CYP2D6 phenotyping

Metoprolol is being used as probe drug to evaluate CYP2D6 activity. Single-dose of metoprolol 100 mg are being administrated orally.

DRUG

Simvastatin 40mg

Single-dose of simvastatin 40 mg are being administrated orally.

DRUG

Midazolam 2 mg for CYP3A4 phenotyping

Midazolam is being used as probe drug to evaluate CYP3A4 activity. Single-dose of midazolam 2 mg are being administrated intravenous.

OTHER

Genotyping

Patients are being genotyped for the main SNP on CYP2C9, ABCB1, SLCO1B1 and CYP2D6 genes using blood samples

Sponsors & Collaborators

• Fundação de Amparo à Pesquisa do Estado de São Paulo

  collaborator OTHER_GOV

• University of Sao Paulo

  collaborator OTHER

• Natalia Valadares de Moraes

  lead OTHER

Principal Investigators

• Wilson Salgado Junior, PhD · University of Sao Paulo

• Jose S dos Santos, PhD · University of Sao Paulo

• Natalia De Moraes, PhD · University of Florida

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-06-01

Primary Completion

2022-08-31

Completion

2023-08-31

FDA Drug

Yes

Countries

• United States

Study Locations