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

Kate Mostoller, Rebecca Wrishko, Lata Maganti, W Joseph Herring, Mariëlle van Zutphen-van Geffen, Kate Mostoller, Rebecca Wrishko, Lata Maganti, W Joseph Herring, Mariëlle van Zutphen-van Geffen

Abstract

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/m2 , 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.

Conflict of interest statement

K.M., R.W., L.M., and W.J.H. are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and may own stock and/or stock options in Merck & Co., Inc., Kenilworth, NJ, USA. M.v.Z.‐v.G. is a paid consultant for Merck Sharp & Dohme (MSD), a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and does not own stock or stock options in Merck & Co., Inc., Kenilworth, NJ, USA.

© 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.

Figures

Figure 1
Figure 1
Mean sugammadex plasma concentration‐time profiles following the administration of a single i.v. dose of sugammadex. We administered 2 mg/kg (a) or 4 mg/kg (b) in patients with morbid obesity. The blue and red lines represent the observed plasma concentrations for patients in the actual body weight (ABW) and ideal body weight (IBW) groups, respectively.
Figure 2
Figure 2
Dose normalized median sugammadex plasma concentration‐time profiles following the administration of a single i.v. dose of sugammadex 2 mg/kg (blue lines) or 4 mg/kg (red lines) in patients with morbid obesity (log‐linear scale). ABW, actual body weight; IBW, ideal body weight.

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Source: PubMed

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