RYGB and Drug Disposition: How to Do Better? Analysis of Pharmacokinetic Studies and Recommendations for Clinical Practice

Abstract

An important issue in the follow-up of patients with bariatric surgery remains to determine whether their therapeutic management should be different after surgery. In this article, we first reviewed all pharmacokinetic studies involving at least four subjects who underwent the Roux-en-Y gastric bypass (RYGB) bariatric surgery. Twenty-five publications were selected and, overall, 25 drugs were studied. Drug solubility and permeability parameters for each drug were defined using different parameters or classifications. Increased rates of oral drug absorption were predominantly observed. Conversely, drug exposure differed from one drug to another. Considering the galenic formulation and the Biopharmaceutics Classification System (BCS) class may help the prediction of oral drug exposure outcome after RYGB. We propose a strategy aiming to guide prescription and drug monitoring in patients with RYGB. But further research is clearly needed due to the unique characteristics of the bariatric population. Priority should be given to drugs that do not have clinical or biological surrogates for dose adaptation.

The influence of bariatric surgery on oral drug bioavailability in patients with obesity: A systematic review

“…Several review papers have assessed the challenges related to changes in drug disposition following bariatric surgery and the consequences on drug dosing . The complex interplay of various factors potentially linked to drug pharmacokinetics such as solubility, permeability, drug‐metabolizing enzymes and transporters, changes in body weight and composition, inflammatory status, and gut microbiota should be considered in relation to pharmacodynamics and efficacy variables that may change after surgery.…”

Laparoscopic Roux‐en‐Y gastric bypass surgery influenced pharmacokinetics of several drugs given as a cocktail with the highest impact observed for CYP1A2, CYP2C8 and CYP2E1 substrates

“…For instance, the decreased gastric volume leads to an increase in the stomach pH (4‐6) and a modified gastric emptying time that can result in an altered rate and extent of oral absorption . Bypassing of the duodenum contributes to a reduction in the absorption surface and can modify intestinal transport and first‐pass metabolism mediated by intestinal CYP enzymes . Finally, the loss of body‐weight can lead to a normalization of the liver fat content, improved hepatic insulin sensitivity and reduced low‐grade inflammation which may alter hepatic clearance and change the distribution of drugs …”

“…The previously published studies have revealed reduced bioavailability in around 46% of investigated drugs and increased bioavailability in 23% of drugs after RYGB . The majority of the studies have been investigations of one or two individual drugs . Fewer studies have investigated RYGB‐associated changes in activities of intestinal/hepatic CYP enzymes .…”

Reduced bioavailability of oral amoxicillin tablets compared to suspensions in Roux‐en‐Y gastric bypass bariatric subjects

“…These patients may present with some drug‐absorption issues because of the reduced length of the small intestine . In particular, very little information is available about AMX absorption in bariatric subjects, which leads to uncertainty about how to prescribe oral antibiotics for this population in order to avoid the risk of therapeutic failure and the development of antimicrobial resistance …”