Clinical pharmacology of rocuronium (ORG 9426): Study of the time course of action, dose requirement, reversibility, and pharmacokinetics

Broek, L. van den; Wierda, J. M. K. H.; Smeulers, Nicky J.; Santen, Gert Jan van; Leclercq, Monique; Hennis, P. J.

doi:10.1016/0952-8180(94)90075-2

Cited by 54 publications

(26 citation statements)

References 30 publications

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“…50 mg of rocuronium bromide). Based on data from clinical studies (3,4,5,6,7), the deceased rocuronium peripheral blood level (0.74 ug/ml, see Table 2) is within the anticipated range following a 50 mg dose. At this level compromised respiration would be expected.…”

Section: Resultsmentioning

confidence: 99%

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Case Report; Rocuronium Related Fatality

Warren

1998

Canadian Society of Forensic Science Journal

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A case report of a fatality involving the suicidal injection of rocuronium, a neuromuscular blocker, is presented. A gas chromatographic (nitrogen/phosphorus detection) method for the quantitative determination of rocuronium in postmortem blood is described. This procedure involves an iodide ion-pair extraction followed by derivatization with MTBSTFA. The rocuronium postmortem blood concentration was found to be 0.74 JJQ/mL. The mass spectrum of the t-BDMS derivative of rocuronium is also provided. RESUMENous presentons un cas de suicide par injection de rocuronium, un bloqueur neuromusculaire. Nous de~rivons une rnetnode d'analyse quantitative de rocuronium dans le sang post mortem par chromatographie gazeuse(detection azote/phosphore). Cette technique implique une extraction par pairage d'ions iodures suivie d'une derivation avec MTPSTFA; la concentration de rocuronium dans I'echantillon de sang post mortem est de 0.74 J,lg/mL. Le spectre de masse du derive t-BDMS du rocuronium est aussi presente.

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Section: Resultsmentioning

confidence: 99%

“…An iv dose of 0.6 mg/kg, administered over 5 seconds, produces a~80% block in an average of 1 min (0.4-6 min) (2). Plasma levels of 0.43 to 2.5 mg/mL have been found in surgical patients following doses of 0.45 to 1.18 mg/kg rocuronium bromide (3,4,5,6,7). All these patients required assisted ventilation.…”

Section: Introductionmentioning

confidence: 99%

Case Report; Rocuronium Related Fatality

Warren

1998

Canadian Society of Forensic Science Journal

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“…While the interaction between muscle relaxants and volatile anesthetics is clearly a pharmacodynamic one, the mechanism of action of nitrous oxide on neuromuscular blocking drugs is still unknown. Volatile anesthetics do not seem to affect the pharmacokinetics of muscle relaxants, and it is generally assumed that nitrous oxide has no effect on the pharmacokinetics of muscle relaxants [16-20]. It has been proposed that nitrous oxide affects the neuromuscular junction directly and independently of its rate of accumulation in the muscle [4] or by altering the transfer of muscle relaxants to the site of action [5].…”

Section: Discussionmentioning

confidence: 99%

Effect of nitrous oxide on cisatracurium infusion demands: a randomized controlled trial

2010

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BackgroundRecent studies have questioned our previous understanding on the effect of nitrous oxide on muscle relaxants, since nitrous oxide has been shown to potentiate the action of bolus doses of mivacurium, rocuronium and vecuronium. This study was aimed to investigate the possible effect of nitrous oxide on the infusion requirements of cisatracurium.Methods70 ASA physical status I-III patients aged 18-75 years were enrolled in this randomized trial. The patients were undergoing elective surgery requiring general anesthesia with a duration of at least 90 minutes. Patients were randomized to receive propofol and remifentanil by target controlled infusion in combination with either a mixture of oxygen and nitrous oxide (Nitrous oxide/TIVA group) or oxygen in air (Air/TIVA group). A 0.1 mg/kg initial bolus of cisatracurium was administered before tracheal intubation, followed by a closed-loop computer controlled infusion of cisatracurium to produce and maintain a 90% neuromuscular block. Cumulative dose requirements of cisatracurium during the 90-min study period after bolus administration were measured and the asymptotic steady state rate of infusion to produce a constant 90% block was determined by applying nonlinear curve fitting to the data on the cumulative dose requirement during the study period.ResultsController performance, i.e. the ability of the controller to maintain neuromuscular block constant at the setpoint and patient characteristics were similar in both groups. The administration of nitrous oxide did not affect cisatracurium infusion requirements. The mean steady-state rates of infusion were 0.072 +/- 0.018 and 0.066 +/- 0.017 mg * kg-1 * h-1 in Air/TIVA and Nitrous oxide/TIVA groups, respectively.ConclusionsNitrous oxide does not affect the infusion requirements of cisatracurium.Trial registrationClinicalTrials.gov NCT01152905; European Clinical Trials Database at http://eudract.emea.eu.int/2006-006037-41.

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“…Based on data from surgical patients and healthy volunteers, the cumulative excretion of rocuronium in the urine over 24 h is in the region of 12-26% and increases to up to 74% after administration of sugammadex 4-8 mg/kg [10][11][12][19][20][21]. Given the importance of renal elimination, the efficacy and safety of sugammadex has been assessed in patients with impaired renal clearance, most of whom were receiving dialysis.…”

Section: Safety and Tolerabilitymentioning

confidence: 99%

“…1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 Studies in volunteers and surgical patients receiving sugammadex to reverse rocuronium-or vecuronium-induced blockade have also demonstrated that the predominant route of elimination for the complex is via the renal route, and in the presence of sugammadex, the major route of elimination of rocuronium changes from the hepatic to the renal route [10][11][12]. Based on data from surgical patients and healthy volunteers, the cumulative excretion of rocuronium in the urine over 24 h is in the region of 12-26% and increases to up to 74% after administration of sugammadex 4-8 mg/kg [10][11][12][19][20][21]. Given the importance of renal elimination, the efficacy and safety of sugammadex has been assessed in patients with impaired renal clearance, most of whom were receiving dialysis.…”

Section: Enrollment and Subject Baseline Characteristicsmentioning

confidence: 99%

Sugammadex is cleared rapidly and primarily unchanged via renal excretion

Peeters

Passier

Smeets

et al. 2011

Biopharm & Drug Disp

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Sugammadex is a modified γ‐cyclodextrin which rapidly reverses rocuronium‐and vecuronium‐induced neuromuscular blockade. Previous studies suggest that sugammadex is mostly excreted unchanged via the kidneys. This single‐center, open‐label, non‐randomized study used 14C‐labeled sugammadex to further investigate the excretion, metabolic and pharmacokinetic (PK) profiles of sugammadex in six healthy male volunteers. 14C‐labeled sugammadex 4 mg/kg (0.025 MBq/kg of 14C‐radioactivity) was administered as a single intravenous bolus. Blood, urine, feces and exhaled air samples were collected at pre‐defined intervals for assessment of sugammadex by liquid chromatography‐mass spectrometry (LC‐MS) and for radioactivity measurements. Adverse events were also assessed. Excretion of sugammadex was rapid with ∼70% of the dose excreted within 6 h and ∼90% within 24 h. Less than 0.02% of radioactivity was excreted in feces or exhaled air. Ninety‐five percent of the radioactivity detected in urine could be attributed to sugammadex, as determined by LC‐MS, suggesting very limited metabolism of sugammadex. LC‐MS analysis of plasma samples found that sugammadex accounted for 100% of total 14C‐radioactivity in the plasma. In general, PK parameters determined from radioactivity and sugammadex plasma concentrations were very similar. Any adverse events were of mild‐to‐moderate intensity, and judged unrelated to sugammadex. These findings demonstrate that sugammadex is cleared rapidly, almost exclusively via the kidney, with minimal or no metabolism. Copyright © 2011 John Wiley & Sons, Ltd.

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Clinical pharmacology of rocuronium (ORG 9426): Study of the time course of action, dose requirement, reversibility, and pharmacokinetics

Cited by 54 publications

References 30 publications

Case Report; Rocuronium Related Fatality

Case Report; Rocuronium Related Fatality

Effect of nitrous oxide on cisatracurium infusion demands: a randomized controlled trial

Sugammadex is cleared rapidly and primarily unchanged via renal excretion

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