Title | Pharmacokinetics of sugammadex in subjects with moderate and severe renal impairment . |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | K Min C, Lasseter KC, Marbury TC, Wrishko RE, Hanley WD, Wolford DG, de Haes JUdo, Reitmann C, Gutstein DE |
Journal | Int J Clin Pharmacol Ther |
Volume | 55 |
Issue | 9 |
Pagination | 746-752 |
Date Published | 2017 Sep |
ISSN | 0946-1965 |
Keywords | Aged, Case-Control Studies, Female, gamma-Cyclodextrins, Half-Life, Humans, Kidney, Male, Middle Aged, Neuromuscular Blockade, Renal Insufficiency |
Abstract | AIMS: Sugammadex rapidly reverses moderate and deep rocuronium- or vecuronium-induced neuromuscular blockade at doses of 4 mg/kg and 2 mg/kg, respectively. Sugammadex is renally eliminated. This study evaluated the pharmacokinetics of sugammadex in subjects with renal impairment versus those with normal renal function. METHODS: This open-label, two-part, phase 1 study included adults with moderate (creatinine clearance (CLcr) 30 - < 50 mL/min) and severe (CLcr < 30 mL/min) renal impairment and healthy controls (CLcr ≥ 80 mL/min). A single intravenous (IV) bolus injection of sugammadex 4 mg/kg was administered into a peripheral vein over 10 seconds directly by straight needle in part 1 (n = 24; 8/group), and via an IV catheter followed by a saline flush in part 2 (n = 18; 6/group). Plasma concentrations of sugammadex were collected after drug administration. Due to dosing issues in part 1, pharmacokinetic parameters were determined for part 2 only. Safety was assessed throughout the study. RESULTS: Pharmacokinetic data were obtained from 18 subjects. Mean sugammadex exposure (AUC0-∞) in subjects with moderate and severe renal impairment was 2.42- and 5.42-times, respectively, that of healthy controls. Clearance decreased and apparent terminal half-life was prolonged with increasing renal dysfunction. Similar Cmax values were observed in subjects with renal impairment and healthy controls. There were no serious adverse events. CONCLUSIONS: Sugammadex exposure is increased in subjects with moderate and severe renal insufficiency due to progressively decreased clearance as a function of worsening renal function. Sugammadex 4 mg/kg was well tolerated in subjects with renal impairment, with a safety profile similar to that of healthy subjects. These results indicate that dose adjustment of sugammadex is not required in patients with moderate renal impairment; however, current safety experience is insufficient to support the use of sugammadex in patients with CLcr < 30 mL/min. . |
DOI | 10.5414/CP203025 |
Alternate Journal | Int J Clin Pharmacol Ther |
PubMed ID | 28679468 |
Submitted by kej2006 on June 6, 2018 - 4:12pm