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Pharmacokinetics of Sugammadex Dosed by Actual and Ideal Body Weight in Patients With Morbid Obesity Undergoing Surgery

This analysis of a published study (NCT03346070) evaluated the pharmacokinetics (PKs) of sugammadex dosed by actual body weight (ABW) or ideal body weight (IBW) for reversal of moderate or deep neuromuscular block (M‐NMB or D‐NMB) in adults with morbid obesity. Adults with body mass index ≥ 40 kg/m(...

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Autores principales: Mostoller, Kate, Wrishko, Rebecca, Maganti, Lata, Herring, W. Joseph, van Zutphen‐van Geffen, Mariëlle
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993252/
https://www.ncbi.nlm.nih.gov/pubmed/33278332
http://dx.doi.org/10.1111/cts.12941
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author Mostoller, Kate
Wrishko, Rebecca
Maganti, Lata
Herring, W. Joseph
van Zutphen‐van Geffen, Mariëlle
author_facet Mostoller, Kate
Wrishko, Rebecca
Maganti, Lata
Herring, W. Joseph
van Zutphen‐van Geffen, Mariëlle
author_sort Mostoller, Kate
collection PubMed
description This analysis of a published study (NCT03346070) evaluated the pharmacokinetics (PKs) of sugammadex dosed by actual body weight (ABW) or ideal body weight (IBW) for reversal of moderate or deep neuromuscular block (M‐NMB or D‐NMB) in adults with morbid obesity. Adults with body mass index ≥ 40 kg/m(2), ABW ≥ 100 kg, and American Society of Anesthesiologists (ASA) Class 3 were stratified by NMB agent (rocuronium or vecuronium) and randomized 1:1:1:1:1 to (i) M‐NMB, sugammadex 2 mg/kg ABW; (ii) M‐NMB, sugammadex 2 mg/kg IBW; (iii) M‐NMB, neostigmine 5 mg + glycopyrrolate 1 mg; (iv) D‐NMB, sugammadex 4 mg/kg ABW; and (v) D‐NMB, sugammadex 4 mg/kg IBW. Plasma samples for sugammadex quantification were collected predose, 2, 5, 15, 60, and 120 minutes, and 4, 6 hours postdose. Natural log PK parameters were analyzed using linear fixed effect model with treatment, mode (ABW and IBW), and mode by treatment interaction as fixed terms. The sugammadex PK profile showed rapid distribution followed by monophasic decline consistent with a two‐compartment model examined by dose and mode. Absolute sugammadex exposures were ~ 50% higher in the ABW vs. IBW group; dose‐independent parameters (clearance and volume of distribution) and terminal half‐life remained constant. Sugammadex PK parameter values increased in dose‐dependent, linear manner following dosing by ABW or IBW, such that PK continues to be predictive across the clinical dose range. In conjunction with previously published results showing faster recovery with ABW vs. IBW dosing across NMB agent and depth of NMB, these PK findings continue to support dosing by ABW in patients with morbid obesity irrespective of depth of NMB.
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spelling pubmed-79932522021-03-29 Pharmacokinetics of Sugammadex Dosed by Actual and Ideal Body Weight in Patients With Morbid Obesity Undergoing Surgery Mostoller, Kate Wrishko, Rebecca Maganti, Lata Herring, W. Joseph van Zutphen‐van Geffen, Mariëlle Clin Transl Sci Research This analysis of a published study (NCT03346070) evaluated the pharmacokinetics (PKs) of sugammadex dosed by actual body weight (ABW) or ideal body weight (IBW) for reversal of moderate or deep neuromuscular block (M‐NMB or D‐NMB) in adults with morbid obesity. Adults with body mass index ≥ 40 kg/m(2), ABW ≥ 100 kg, and American Society of Anesthesiologists (ASA) Class 3 were stratified by NMB agent (rocuronium or vecuronium) and randomized 1:1:1:1:1 to (i) M‐NMB, sugammadex 2 mg/kg ABW; (ii) M‐NMB, sugammadex 2 mg/kg IBW; (iii) M‐NMB, neostigmine 5 mg + glycopyrrolate 1 mg; (iv) D‐NMB, sugammadex 4 mg/kg ABW; and (v) D‐NMB, sugammadex 4 mg/kg IBW. Plasma samples for sugammadex quantification were collected predose, 2, 5, 15, 60, and 120 minutes, and 4, 6 hours postdose. Natural log PK parameters were analyzed using linear fixed effect model with treatment, mode (ABW and IBW), and mode by treatment interaction as fixed terms. The sugammadex PK profile showed rapid distribution followed by monophasic decline consistent with a two‐compartment model examined by dose and mode. Absolute sugammadex exposures were ~ 50% higher in the ABW vs. IBW group; dose‐independent parameters (clearance and volume of distribution) and terminal half‐life remained constant. Sugammadex PK parameter values increased in dose‐dependent, linear manner following dosing by ABW or IBW, such that PK continues to be predictive across the clinical dose range. In conjunction with previously published results showing faster recovery with ABW vs. IBW dosing across NMB agent and depth of NMB, these PK findings continue to support dosing by ABW in patients with morbid obesity irrespective of depth of NMB. John Wiley and Sons Inc. 2020-12-16 2021-03 /pmc/articles/PMC7993252/ /pubmed/33278332 http://dx.doi.org/10.1111/cts.12941 Text en © 2020 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research
Mostoller, Kate
Wrishko, Rebecca
Maganti, Lata
Herring, W. Joseph
van Zutphen‐van Geffen, Mariëlle
Pharmacokinetics of Sugammadex Dosed by Actual and Ideal Body Weight in Patients With Morbid Obesity Undergoing Surgery
title Pharmacokinetics of Sugammadex Dosed by Actual and Ideal Body Weight in Patients With Morbid Obesity Undergoing Surgery
title_full Pharmacokinetics of Sugammadex Dosed by Actual and Ideal Body Weight in Patients With Morbid Obesity Undergoing Surgery
title_fullStr Pharmacokinetics of Sugammadex Dosed by Actual and Ideal Body Weight in Patients With Morbid Obesity Undergoing Surgery
title_full_unstemmed Pharmacokinetics of Sugammadex Dosed by Actual and Ideal Body Weight in Patients With Morbid Obesity Undergoing Surgery
title_short Pharmacokinetics of Sugammadex Dosed by Actual and Ideal Body Weight in Patients With Morbid Obesity Undergoing Surgery
title_sort pharmacokinetics of sugammadex dosed by actual and ideal body weight in patients with morbid obesity undergoing surgery
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993252/
https://www.ncbi.nlm.nih.gov/pubmed/33278332
http://dx.doi.org/10.1111/cts.12941
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