LAUSR

Roux-en-Y gastric bypass (RYGB) is one of the most common surgical treatments for obesity due to the effective long-term weight loss and remission of associated comorbidities. Carvedilol, a third-generation β-blocker, is prescribed to treat cardiovascular diseases. This drug is a weak base with low and pH-dependent solubility and dissolution, and high permeability. As the changes in the gastrointestinal tract anatomy and physiology after RYGB can potentially affect drug pharmacokinetics (PK), this study aimed to assess the effect of RYGB on the PK of carvedilol enantiomers. Non-obese [n = 15, body mass index (BMI) < 25 kg/m2 ], obese (n = 19, BMI ≥ 30) and post-RYGB subjects submitted to surgery for at least 6 months (n = 19) were investigated. All subjects were administered with a single oral dose of 25 mg racemic-carvedilol, and blood was sampled for up to 24 hours. Plasma concentrations of (R)- and (S)-carvedilol were determined by LC-MS/MS. The maximum plasma concentration (Cmax ) and the area under the plasma concentration-time curve (AUC) of (R)-carvedilol were 2 to 3-fold higher than (S)-carvedilol in all groups. Obese subjects have shown reduced Cmax of (R)- and (S)-carvedilol without changing the AUC. Post-RYGB subjects presented a 3.5-fold reduction in the Cmax of the active (S)-carvedilol and a 1.9 reduction in the AUC∞ compared to non-obese subjects. The time to reach Cmax (tmax ) of (S)-carvedilol increased 2.5-fold in post-RYGB subjects compared to obese or non-obese. Although the beta-blockade response was not assessed, the reduced exposure to carvedilol in subjects post-RYGB may be clinically relevant and require dose adjustment. This article is protected by copyright. All rights reserved.