Noveron Mechanism of Action

Pharmacotherapeutic group: Neuromuscular Blocking Agents. ATC code: M03AC09.
Pharmacology: Pharmacodynamics: Mechanism of Action: Rocuronium bromide is a fast onset, intermediate acting non-depolarising neuromuscular blocking agent (blocking acetylcholine from binding to receptors on motor endplate inhibiting depolarization), possessing all of the characteristic pharmacological actions of this class of drugs (curariform). It acts by competing for nicotinic cholinoceptors at the motor end-plate.
Pharmacodynamic effects: The ED₉₀ (dose required to produce 90% depression of the twitch response of the thumb to stimulation of the ulnar nerve) during intravenous anaesthesia is approximately 0.3 mg/kg rocuronium bromide. The ED95 in infants is lower than in adults and children (0.25, 0.35 and 0.40 mg/kg respectively).
The clinical duration (the duration until spontaneous recovery to 25% of control twitch height) with 0.6 mg/kg rocuronium bromide is 30-40 minutes. The total duration (time until spontaneous recovery 90% of control twitch height) is 50 minutes. The mean time of spontaneous recovery of twitch response from 25 to 75% (recovery index) after a bolus dose of 0.6 mg/kg rocuronium bromide is 14 minutes. With lower dosages of 0.3-0.45 mg/kg rocuronium bromide (1-1½ x ED90), onset of action is slower and duration of action is shorter. With high dose of 2 mg/kg, clinical duration is 110 minutes.
Intubation during routine anesthesia: Within 60 seconds after intravenous administration of a dose of 0.6 mg/kg rocuronium bromide (2 x ED90 under intravenous anaesthesia), adequate intubation conditions can be achieved in nearly all patients. In 80% of these patients intubation conditions are rated excellent. Within 2 minutes general muscle paralysis adequate for any type of procedure is established. After administration of 0.45 mg/kg rocuronium bromide, acceptable intubation conditions are reached after 90 seconds.
Rapid sequence induction: During rapid sequence induction of anaesthesia under propofol or fentanyl/thiopental anaesthesia, adequate intubation conditions are achieved within 60 seconds in 93% and 96% of the patients respectively, after administration of a dose of 1.0 mg/kg rocuronium bromide. Of these, 70% are rated excellent. The clinical duration with this dose approaches 1 hour, at which time the neuromuscular block can be safely reversed. After administration of a dose of 0.6 mg/kg rocuronium bromide, adequate intubation conditions are achieved within 60 seconds in 81% and 75% of the patients during a rapid sequence induction technique with propofol or fentanyl/thiopental, respectively.
Paediatric population: Mean onset time in infants, toddlers and children at an intubation dose of 0.6 mg/kg is slightly shorter than adults. (See Table 1.)

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Geriatric patients and patients with hepatic and/or biliary tract disease and/or renal failure: The duration of action of maintenance doses of 0.15 mg/kg rocuronium bromide might be longer under enflurane and isoflurane anaesthesia in geriatric and in patients with hepatic and/or renal disease (approximately 20 minutes) than in patients without impairment of excretory organ function under intravenous anaesthesia (approximately 13 minutes). No accumulation of effect (progressive increase in duration of action) with repetitive maintenance dosing at the recommended level has been observed.
Intensive care unit: Following continuous infusion in the Intensive Care Unit, the time to recovery of the train of four ratio to 0.7 depends on the level of block at the end of the infusion. After a continuous infusion for 20 hours or more the median (range) time between return of T₂ to train of four stimulation and recovery of the train of four ratio to 0.7 approximates 1.5 (1-5) hours in patients without multiple organ failure and 4 (1-25) hours in patients with multiple organ failure.
Cardiovascular surgery: In patients scheduled for cardiovascular surgery the most common cardiovascular changes during the onset of maximum block following 0.6-0.9 mg/kg rocuronium bromide are a slight and clinically insignificant increase in heart rate up to 9% and an increase in mean arterial blood pressure up to 16% from the control values.
Reversal of muscle relaxation: Administration of acetylcholinesterase inhibitors, such as neostigmine, pyridostigmine or edrophonium, antagonises the action of rocuronium bromide.
Pharmacokinetics: Adult: Onset of action: Good intubation conditions within 1-2 minutes (depending on dose administered) maximum neuromuscular blockade within 4 minutes.
Duration: 30 minutes (with standard dose, increases with higher doses and inhalational anesthetic agents; patient age dependent).
Distribution: Volume of distribution is 0.22-0.26 L/kg.
Protein binding: Approximately 30%.
Metabolism: Minimally hepatic, converted to 17-desacetylrocuronium as main metabolite (5%-10% activity of parent drug).
Half-life elimination: Alpha elimination: 1-2 minutes.
Beta elimination Adults: 1.4-2.4 hours.
Excretion: Feces 31% and Urine 26%.
Paediatric population: The pharmacokinetics parameters of typical paediatrics within each age group are summarized as follows: See Table 2.

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Geriatric patients and patients with hepatic and/or biliary tract disease and/or renal failure: In controlled studies the plasma clearance in geriatric patients and in patients with renal dysfunction was reduced, in most studies however without reaching the level of statistical significance. In patients with hepatic disease, the mean elimination half-life is prolonged by 30 minutes and the mean plasma clearance is reduced by 1 mL/kg/min.
Intensive care unit: When administered as a continuous infusion to facilitate mechanical ventilation for 20 hours or more, the mean elimination half-life and the mean (apparent) volume of distribution at steady state are increased. A large between patient variability is found in controlled clinical studies, related to nature and extent of (multiple) organ failure and individual patient characteristics. In patients with multiple organ failure a mean (±SD) elimination half-life of 21.5 (±3.3) hours, a volume of distribution at steady state of 1.5 (±0.8) L/kg and a plasma clearance of 2.1 (±0.8) mL/kg/min were found.