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

Overview

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.

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.

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