Analysis of the Influence of Gastric By-Pass on the Pharmacokinetics of Common Drugs (ABSORGYP)

Lack of knowledge of digestive absorption of drugs used in metabolic syndrome (MS) before and after gastric by-pass (GBP) in obese patients. The main objective is to study the changes in apparent clearance of candesartan, amlodipine, metformin and rosuvastatin, used in the treatment of metabolic syndrome in obese patients, between the preoperative period and 1 and 6 months after the performance of a GBP.

Study Overview

• Status: Not yet recruiting
• Conditions: Bypass Bariatric Surgery
• Intervention / Treatment: Other: pharmacokinetic study

Detailed Description

The aim of this study is to investigate the pharmacokinetics of some of the most frequently prescribed oral drugs in hospital and outpatient medicine, in patients undergoing GBP surgery for obesity associated with metabolic syndrome. Paradoxically, despite their frequency of use, very few data, contradictory data or no data at all characterize the molecules we wish to study.

The number of patients undergoing GBP surgery is growing rapidly, as their life expectancy reaches that of the general population once their weight has normalized. However, while weight loss induced by surgery can improve, and more rarely cure, the comorbidities associated with metabolic syndrome, the majority of patients will need to continue or modify their treatments.

It is therefore essential to know the pharmacokinetics of the antihypertensive, lipid-lowering and hypoglycemic drugs they will be taking throughout their lives, in order to adapt their dosage if necessary, or even to change therapeutic class if their absorption is insufficient after GBP.

Moreover, as some studies have shown, the pharmacokinetics of many molecules are likely to vary over time in these patients (19), probably as a result of weight loss itself, but also possibly due to adaptive phenomena in the digestive tract. Studying the pharmacokinetics of the molecules used in the usual treatment of metabolic syndrome in most obese patients should make it possible to: target the preferred sites of absorption in the digestive tract of the molecules studied, study the variations in absorption linked to GBP but also the pharmacokinetic changes linked to weight loss as a function of time. In fact, metabolic capacity may be both decreased and increased in obese patients compared to healthy subjects (20,21), so that drug clearance may both increase and decrease after weight normalization. It is therefore difficult to predict the pharmacokinetics of drugs immediately or long after GYP. The results obtained should make it possible to adapt treatment in these patients, both in terms of changing the dosage administered and in the choice of molecules.

• Study Type: Interventional
• Enrollment (Estimated): 64
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Andrea LAZZATI; Phone Number: 06 67 47 66 03; Email: andrea.lazzati@aphp.fr
• Study Contact Backup: Name: Vicent JULLIEN, Pr; Phone Number: 01 48 02 62 28; Email: vincent.jullien@aphp.fr

Study Locations

• France
  • Bobigny, France, 93000
    • Service de chirurgie digestive, bariatrique et endocrinienne
    • Contact: Andrea LAZZATI

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years
• Patients having undergone a complete bariatric course, eligible for bariatric surgery after validation of the operative indication by a multidisciplinary RCP dedicated to obesity, in accordance with HAS criteria: morbid obesity with BMI > 40 kg/m2 or severe obesity with BMI >35Kg/m2
• Patients with a comorbidity linked to one of the elements of metabolic syndrome that can be improved by surgery: type 2 diabetes, hypertension, dyslipidemia.

• Patients treated pre-operatively for at least 2 weeks with one or more of the molecules designed to control metabolic syndrome and selected for our study:

  • Antihypertensive: amlodipine; candesartan,
  • Hypolipidemic: rosuvastatin
  • Hypoglycemic agent: metformin
• Patients scheduled for Y-shaped gastric bypass surgery
• Membership of a social security scheme

Exclusion Criteria:

• History of restrictive bariatric surgery (sleeve)
• History of renal or hepatocellular insufficiency
• Patient undergoing treatment or having stopped treatment within the last month with a drug that may alter the clearance of the molecules studied: enzyme inducer or inhibitor (boosted antiproteases, macrolides, azole antifungals, grapefruit juice, rifampicin, rifabutin, phenobarbital, phenytoin, St John's wort), probenecid, non-steroidal anti-inflammatory drugs, etc.
• Patients treated with a drug that may alter the bioavailability of associated drugs: antacids containing aluminium or magnesium hydroxide, gastric dressings, etc.
• Patients for whom it is impossible to give informed consent (language barrier)
• Patients taking part in another interventional clinical study
• Patients under legal protection (guardianship, curatorship)
• Pregnant or breast-feeding women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Patients eligible for bypass bariatric surgery and treated for metabolic syndrome; 6 samples will be taken on the same day (T0, i.e. just before taking the drug, then T30 minutes, T1h, T2h, T4h, T7h after taking the drug).	Other: pharmacokinetic study; Multicenter pharmacokinetic study of the bioavailability of four compounds in GBP patients: candesartan, amlodipine, metformin and rosuvastatin.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The main objective is to study the changes in apparent clearance of candesartan, amlodipine, metformin and rosuvastatin, used in the treatment of metabolic syndrome in obese patients	Difference in apparent clearance of study drugs between preoperative and postoperative phases at 1 month after surgery	preoperative and postoperative phases at 1 month after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine changes in apparent clearance at 6 months after gastric bypass surgery compared with the pre-operative phase	Difference in apparent clearance of the 4 drugs studied between preoperative and postoperative phases at 6 months after gastric bypass surgery	pre-operative phase and 1 and 6 months after surgery
Explain changes in apparent clearance as a function of weight loss	Change in apparent clearance as a function of body weight loss, measured by bioelectrical impedancemetry	pre-operative phase and 1 and 6 months after surgery
Explain changes in apparent clearance as a function of changes in the fat/lean mass ratio	Change in apparent clearance as a function of change in body fat/lean mass ratio, measured by bioelectrical impedancemetry	pre-operative phase and 1 and 6 months after surgery
Determine changes in apparent volumes of distribution between the pre-operative phase and 1 and 6 months after surgery	Differences in apparent volume of distribution values between the pre-operative phase and 1 month, then 6 months after surgery	pre-operative phase and 1 and 6 months after surgery
Explain changes in apparent volumes of distribution as a function of body weight loss	Change in apparent volume of distribution as a function of body weight loss	pre-operative phase and 1 and 6 months after surgery
Explain changes in apparent volumes of distribution as changes in body fat	Change in apparent volume of distribution as change in body fat/lean body mass ratio	pre-operative phase and 1 and 6 months after surgery
Based on the results obtained, recommend any necessary changes in dosage or therapeutic class for these molecules	Dosages calculated to achieve the AUCs calculated before and 6 months after surgery, as well as the AUCs described for non-obese patients, at 1 month and 6 months post-surgery	pre-operative phase and 1 and 6 months after surgery

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Andrea LAZZATI, Assistance Publique de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: May 30, 2024
• First Submitted That Met QC Criteria: June 10, 2024
• First Posted (Actual): June 14, 2024

Study Record Updates

• Last Update Posted (Actual): June 14, 2024
• Last Update Submitted That Met QC Criteria: June 10, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: bypass bariatric surgery, metabolic syndrome
• Other Study ID Numbers: APHP230873

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No