Pharmacokinetics of Rocuronium After Bolus and Continuous Infusion During Halothane Anaesthesia

“…The use of rocuronium has been described in dogs under clinical conditions with incremental dosing for maintenance of block (Dugdale et al. 2002) and by infusion (Auer 2002) and in humans with incremental dosing and infusions (McCoy et al. 1996; Saldien et al.…”

Section: Introductionmentioning

confidence: 99%

Use of rocuronium administered by continuous infusion in dogs

Alderson

Senior

Jones

et al. 2007

Veterinary Anaesthesia and Analgesia

View full text Add to dashboard Cite

“…Two-compartmental models, instead of the previously applied three-compartmental models, for rocuronium, sugammadex and the complex were sufficient to describe the concentrations in the therapeutic concentration range. A two-compartmental model for rocuronium PK has been applied previously [23,24,40]. The bias observed at the extremes of the rocuronium concentration range, at a large distance from the EC50, does not translate to effects in NMB and was therefore judged clinically irrelevant and acceptable.…”

mentioning

confidence: 99%

Population pharmacokinetic–pharmacodynamic analysis for sugammadex‐mediated reversal of rocuronium‐induced neuromuscular blockade

Kleijn¹,

Zollinger

Heuvel

et al. 2011

Brit J Clinical Pharma

View full text Add to dashboard Cite

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Pharmacokinetics and pharmacodynamics of rocuronium are well known.• A mechanistical pharmacokineticpharmacodynamic model based on limited data describing rocuronium and sugammadex pharmacokinetics has been published.• However, the available pharmacokineticpharmacodynamic model for the effects of sugammadex on rocuronium-induced neuromuscular blockade has limited predictive power. WHAT THIS STUDY ADDS• A pharmacokinetic-pharmacodynamic model is described for rocuronium and sugammadex, based on physiological principles and on data covering a wide range of ages and renal function. From this model, more accurate predictions can be made about sugammadex-mediated reversal of rocuronium-induced neuromuscular blockade, in unexplored regimens or populations. AIMSAn integrated population pharmacokinetic-pharmacodynamic model was developed with the following aims: to simultaneously describe pharmacokinetic behaviour of sugammadex and rocuronium; to establish the pharmacokinetic-pharmacodynamic model for rocuronium-induced neuromuscular blockade and reversal by sugammadex; to evaluate covariate effects; and to explore, by simulation, typical covariate effects on reversal time. METHODSData (n = 446) from eight sugammadex clinical studies covering men, women, non-Asians, Asians, paediatrics, adults and the elderly, with various degrees of renal impairment, were used. Modelling and simulation techniques based on physiological principles were applied to capture rocuronium and sugammadex pharmacokinetics and pharmacodynamics and to identify and quantify covariate effects. RESULTSSugammadex pharmacokinetics were affected by renal function, bodyweight and race, and rocuronium pharmacokinetics were affected by age, renal function and race. Sevoflurane potentiated rocuronium-induced neuromuscular blockade. Posterior predictive checks and bootstrapping illustrated the accuracy and robustness of the model. External validation showed concordance between observed and predicted reversal times, but interindividual variability in reversal time was pronounced. Simulated reversal times in typical adults were 0.8, 1.5 and 1.4 min upon reversal with sugammadex 16 mg kg -1 3 min after rocuronium, sugammadex 4 mg kg -1 during deep neuromuscular blockade and sugammadex 2 mg kg -1 during moderate blockade, respectively. Simulations indicated that reversal times were faster in paediatric patients and slightly slower in elderly patients compared with adults. Renal function did not affect reversal time. CONCLUSIONSSimulations of the therapeutic dosing regimens demonstrated limited impact of age, renal function and sevoflurane use, as predicted reversal time in typical subjects was always <2 min.

show abstract

“…Cooper et al . reported in patients with normal renal function during isoflurane anaesthesia [7] values of 207 mL kg −1 , 3.7 mL kg −1 min −1 , 97.2 min and 58.3 min; McCoy and colleagues [9] found in patients under halothane anaesthesia 212 mL kg −1 , 3.3 mL kg −1 min −1 , 85.6 min and 67.2 min, for steady‐state volume, clearance, elimination half‐life and mean residence time (MRT). In the present study, the mean values in the two different groups ranged between 169 and 208 mL kg −1 steady‐state volume, 3.62 and 3.89 mL kg −1 min −1 clearance, 70.3 and 75.5 min elimination half‐life and 51.4 and 53.2 min MRT.…”

Section: Discussionmentioning

confidence: 99%

“…used isoflurane anaesthesia, which is known to potentiate rocuronium relative to opioid‐based anaesthesia [11], giving a plasma concentration of only 891 ng mL −1 rocuronium at 25% recovery of T1. McCoy and colleagues [9] reported a plasma concentration of 1287 ng mL −1 rocuronium at 25% recovery of T1 under halothane anaesthesia.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of rocuronium bromide in obese female patients

et al. 1999

View full text Add to dashboard Cite

Following administration of 0.6 mg kg-1 rocuronium, the pharmacokinetics and the pharmacodynamics were studied in six obese and six control (normal weight) patients receiving balanced anaesthesia. Twelve gynaecological patients were allocated into two groups, according to body mass index (normal weight: body mass index: 20-24, obese weight: body mass index > 28). Venous plasma concentrations were determined by high-pressure liquid chromatography before administration of rocuronium, at 1, 2, 4, 6, 8, 10, 15, 20, 25, 30, 35, 40, 48, 60, 75, 120, 180, 240, 300, 360 and 420 min after administration of rocuronium and at recovery of single twitch to 25% and 75% of control twitch height. Onset time was shorter (NS) in the obese compared with normal weight (obese weight: 65 +/- 16, normal weight: 100 +/- 39 s, mean +/- SD). Duration 25% (obese weight: 29.5 +/- 5.3, normal weight: 28.4 +/- 5.3 min) and spontaneous recovery time (obese weight: 12.6 +/- 2.7, normal weight: 12.5 +/- 2.3 min) did not show any differences between the two groups. The pharmacokinetics of rocuronium were comparable in the two groups. The volume of distribution at steady state Vss (mL kg-1) was 208 +/- 56 in normal weight and 169 +/- 37 in obese weight. Distribution (T1/2 alpha) and elimination half-life (T1/2 beta) as well as mean residence time were 15.6 +/- 3.7, 70.3 +/- 23.9 and 53.2 +/- 9.8 min in normal weight and 16.9 +/- 3.8, 75.5 +/- 25.5 and 51.1 +/- 18.9 min in obese weight, respectively. Also, no differences were observed in plasma clearance (3.89 +/- 0.58 in normal weight and 3.62 +/- 1.42 mL kg-1 min-1 obese weight). This study indicates that the pharmoacodynamics and pharmacokinetics of rocuronium are in female patients not altered by obesity.

show abstract

Pharmacokinetics of Rocuronium After Bolus and Continuous Infusion During Halothane Anaesthesia

Cited by 4 publications

References 0 publications

Use of rocuronium administered by continuous infusion in dogs

Use of rocuronium administered by continuous infusion in dogs

Population pharmacokinetic–pharmacodynamic analysis for sugammadex‐mediated reversal of rocuronium‐induced neuromuscular blockade

Pharmacokinetics of rocuronium bromide in obese female patients

Contact Info

Product

Resources

About