Impact of Roux-en-Y gastric bypass bariatric surgery on System Pharmacology: single-dose cross-over pharmacokinetic study of simvastatin and carvedilol

• Grant number: 18/06569-9
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2019
• End date: August 31, 2022
• Field of knowledge: Biological Sciences - Pharmacology - Clinical Pharmacology
• Principal Investigator: Cristiane Masetto de Gaitani
• Grantee: Cristiane Masetto de Gaitani
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Ajith Kumar Sankarankutty ; Cristiane Masetto de Gaitani ; José Sebastião dos Santos ; Wilson Salgado Junior

Abstract

The impact of anatomical changes of the gastrointestinal tract resulting from bariatric surgery on pharmacokinetics are due to changes in gastric and intestinal pH, reduction in intestinal transit time, changes in the surface area available for absorption and changes in the abundance of enzymes and drug carriers. Physiologycally based pharmacokinetic (PBPK) models have been developed to predict the effect of bariatric surgery on pharmacokinetics. PBPK models are promising for individualized pharmacological therapy, since they may predict pharmacokinetic parameters for drugs clinically available or for new drug candidates. However, limitations of the model are related to the few clinical studies performed in this population with appropriate design. This study proposes to perform two cross-over studies to investigate the kinetic disposition of simvastatin (Study A) and carvedilol in 3 steps: before, 4-6 months after surgery, and 10-12 months after Roux-en Y gastric bypass bariatric surgery (RYGB). The expression of CYP3A4 and P-glycoprotein (mRNA) will be evaluated in intestinal biopsies collected during preoperative endoscopy, during RYGB and post-surgery. The data from these studies will be used to built mechanistic models to predict the kinetic disposition in complex patients, since bariatric RYGB surgery can significantly alter Systems Pharmacology. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PAVAN, MARCELLA; YAMAMOTO, PRISCILA; DA SILVA, RODRIGO MOREIRA; JUNIOR, WILSON SALGADO; DOS SANTOS, JOSE; KEMP, RAFAEL; SANKARANKUTTY, AJITH; DE MORAES, NATALIA; DE GAITANI, CRISTIANE. Chemometric optimization of salting-out assisted liquid-liquid extraction (SALLE) combined with LC-MS/MS for the analysis of carvedilol enantiomers in human plasma: Application to clinical pharmacokinetics. JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, v. 1205, p. 9-pg., 2022-08-01. (18/06569-9)