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

Not Applicable

Not yet recruiting

• Conditions: Bypass Bariatric Surgery
• Interventions: Other: pharmacokinetic study

• Registration Number: NCT06460896
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

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.

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 Timeline

• Status Verified: 2024-05
• Study First Submitted: 2024-05-30
• Study First Submitted QC: 2024-06-10
• Last Update Submitted: 2024-06-10
• Study First Posted: 2024-06-14
• Last Update Posted: 2024-06-14
• Study Start: 2024-09
• Primary Completion: 2027-09
• Study Completion: 2027-09

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 64

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Patients eligible for bypass bariatric surgery and treated for metabolic syndrome	pharmacokinetic study	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).

Primary Outcome Measures

Name	Time	Method
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	preoperative and postoperative phases at 1 month after surgery	Difference in apparent clearance of study drugs between preoperative and postoperative phases at 1 month after surgery

Secondary Outcome Measures

Name	Time	Method
Explain changes in apparent clearance as a function of weight loss	pre-operative phase and 1 and 6 months after surgery	Change in apparent clearance as a function of body weight loss, measured by bioelectrical impedancemetry
Explain changes in apparent clearance as a function of changes in the fat/lean mass ratio	pre-operative phase and 1 and 6 months after surgery	Change in apparent clearance as a function of change in body fat/lean mass ratio, measured by bioelectrical impedancemetry
Based on the results obtained, recommend any necessary changes in dosage or therapeutic class for these molecules	pre-operative phase and 1 and 6 months after surgery	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
Determine changes in apparent clearance at 6 months after gastric bypass surgery compared with the pre-operative phase	pre-operative phase and 1 and 6 months after surgery	Difference in apparent clearance of the 4 drugs studied between preoperative and postoperative phases at 6 months after gastric bypass surgery
Determine changes in apparent volumes of distribution between the pre-operative phase and 1 and 6 months after surgery	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
Explain changes in apparent volumes of distribution as a function of body weight loss	pre-operative phase and 1 and 6 months after surgery	Change in apparent volume of distribution as a function of body weight loss
Explain changes in apparent volumes of distribution as changes in body fat	pre-operative phase and 1 and 6 months after surgery	Change in apparent volume of distribution as change in body fat/lean body mass ratio

Trial Locations

Locations (1)

Service de chirurgie digestive, bariatrique et endocrinienne; 🇫🇷 Bobigny, France