Effect of Roux-En-Y Gastric Bypass in the Pharmacokinetics of (R)-Carvedilol and (S)-Carvedilol.

Autor: Yamamoto PA; School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil.; Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, FL, USA., Cristofoletti R; Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, FL, USA., Vozmediano V; Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, FL, USA., de Gaitani CM; School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil., da Silva RM; School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil., Kemp R; School of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil., Sankarankutty AK; School of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil., Salgado Junior W; School of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil., Santos JSD; School of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil., de Moraes NV; Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, FL, USA.
Jazyk: angličtina
Zdroj: Journal of clinical pharmacology [J Clin Pharmacol] 2023 Jul; Vol. 63 (7), pp. 838-847. Date of Electronic Publication: 2023 Apr 06.
DOI: 10.1002/jcph.2221
Abstrakt: Roux-en-Y gastric bypass 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 roux-en-Y gastric bypass can potentially affect drug pharmacokinetics, this study aimed to assess the effect of roux-en-Y gastric bypass on the pharmacokinetics of carvedilol enantiomers. Nonobese (n = 15, body mass index < 25 kg/m 2 ), obese (n = 19, body mass index ≥ 30), and post-roux-en-Y gastric bypass subjects submitted to surgery for at least 6 months (n = 19) were investigated. All subjects were administered 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 liquid chromatography-tandem mass spectrometry. The maximum plasma concentration (C max ) 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 C max of (R)- and (S)-carvedilol without changing the AUC. Post-roux-en-Y gastric bypass subjects presented a 3.5-fold reduction in the C max of the active (S)-carvedilol and a 1.9 reduction in the AUC from time 0 to infinity compared to nonobese subjects. The time to reach C max of (S)-carvedilol increased 2.5-fold in post-roux-en-Y gastric bypass subjects compared to obese or nonobese. Although the β-blockade response was not assessed, the reduced exposure to carvedilol in subjects post-roux-en-Y gastric bypass may be clinically relevant and require dose adjustment.
(© 2023, The American College of Clinical Pharmacology.)
Databáze: MEDLINE
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