Pharmacokinetics of sugammadex in subjects with moderate and severe renal impairmentâ©.
Int J Clin Pharmacol Ther
; 55(9): 746-752, 2017 Sep.
Article
em En
| MEDLINE
| ID: mdl-28679468
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.â©.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Gama-Ciclodextrinas
/
Insuficiência Renal
/
Rim
Tipo de estudo:
Observational_studies
Limite:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Int J Clin Pharmacol Ther
Assunto da revista:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Ano de publicação:
2017
Tipo de documento:
Article