Disease relevance of C07556

• The authors conclude that renal failure and renal transplantation alter the distribution but not the clearance of rocuronium [1].
• This increased onset time was linearly correlated to the increased central volume of distribution of rocuronium in cirrhosis [2].
• 7. With the exception of rocuronium there was a significant interaction with m2 muscarinic receptors with all NMBD's at clinically achievable concentrations suggesting that the brady/tachycardias associated with these agents may result from an interaction with cardiac muscarinic receptors [3].
• RESULTS: All eight pigs of the myasthenic group developed clinical signs of myasthenia gravis (muscle weakness) and showed increased sensitivity toward rocuronium [4].
• CONCLUSIONS: Despite prolonged hypothermic ischemia, the newly transplanted liver eliminates rocuronium as well as the diseased native liver (and comparably with historical control values) [5].

Psychiatry related information on C07556

• Huntington's chorea: use of rocuronium [6].

High impact information on C07556

• Pharmacokinetics and pharmacodynamics of rocuronium at the vocal cords and the adductor pollicis in humans [7].
• By forming host-guest complexes with rocuronium, these cyclodextrin derivatives reverse the muscle relaxation induced by rocuronium in vitro and in vivo and therefore can be used as reversal agents of the neuromuscular blocker to assist rapid recovery of patients after surgery [8].
• From a small series of compounds 20c,e are identified as effective non-depolarizing NMB agents in vitro and in vivo in anesthetized cats and Rhesus monkeys with potencies similar to those of the clinical reference compounds rocuronium (4) and suxamethonium (2) (monkey ED(90) = 0.68, 0.23, 0.16, 5.04 micromol/kg, respectively) [9].
• Similarly, the decrease in diaphragm type IIx/b fiber dimensions was more pronounced after mechanical ventilation with rocuronium treatment than with saline treatment (-38% and -29%, respectively; p < .001 vs. control) [10].
• CONCLUSIONS: Infusion of rocuronium during controlled mechanical ventilation leads to further deterioration of diaphragm function, additional atrophy of type IIx/b fibers, and an increase in MURF-1 messenger RNA in the diaphragm, which suggests an activation of the ubiquitin-proteasome pathway [10].

Chemical compound and disease context of C07556

• The incidence of the reports containing anaphylaxis terms did not differ between vecuronium and rocuronium in the U.S. but were significantly different for foreign reports (P < 0.001) [11].
• These large doses of rocuronium may be useful in, for instance, head trauma or open globe injuries if succinylcholine is contraindicated [12].
• The pharmacodynamics of an initial dose of 0.6 mg.kg-1 rocuronium followed by three maintenance doses of 0.15 mg.kg-1 were studied during nitrous oxide/oxygen/isoflurane anaesthesia in patients with normal renal function (n = 12) and chronic renal failure (n = 12) [13].
• The standardized rightward shifts in early and late sepsis were largest for pancuronium, second largest for rocuronium, and smallest for d-tubocurarine (5.741, 2.979, and 1.660 times in late sepsis, respectively; P < 0.01 each by ANOVA and the Scheffe F test) [14].
• After administration of thiopentone and rocuronium in two patients, temporary erythema occurred, one along the site of injection and the other on the chest wall [15].

Biological context of C07556

• Recirculatory pharmacokinetics and pharmacodynamics of rocuronium in patients: the influence of cardiac output [16].
• Comparative clinical pharmacology of rocuronium, cisatracurium, and their combination [17].
• Although elimination kinetics are unchanged in patients with cirrhosis, rocuronium recovery time is prolonged in cirrhotic patients [2].
• Bioavailability of intramuscular rocuronium in infants and children [18].
• Rocuronium had no clinically significant effect on maternal heart rate or arterial pressure [15].

Anatomical context of C07556

• The reversal can be explained by the rapid transfer of free rocuronium from the effect compartment (neuromuscular junction) to the central compartment, in which it is bound to Org 25969 [19].
• Do pipecuronium and rocuronium affect human bronchial smooth muscle [20]?
• Characterization of the uptake of rocuronium and digoxin in human hepatocytes: carrier specificity and comparison with in vivo data [21].
• In cRNA-injected Xenopus laevis oocytes, all three carriers mediated uptake of the known type II model compounds N-(4, 4-azo-n-pentyl)-21-deoxy-ajmalinium and rocuronium, whereas the newly synthesized type II model compounds N-methyl-quinine and N-methyl-quinidine were transported only by the human organic anion transporting polypeptide [22].
• Rocuronium 0.6 mg/kg was then administered, and neuromuscular transmission was assessed using electromyographic response to train-of-four stimulation of the ulnar nerve at the wrist every 10 s [23].

Associations of C07556 with other chemical compounds

• CONCLUSIONS: Both 1.2 mg/kg rocuronium (three times the ED95) and 2 mg/kg succinylcholine provide 90% neuromuscular block within 45 s in 95% of children [24].
• RESULTS: The calculated ED50 values and their 95% confidence intervals were 125 (122-129) and 37 (36-38) micrograms.kg-1 for the rocuronium and mivacurium groups, respectively [25].
• After premedication with 0.04 mg/kg intravenous midazolam, anesthesia was induced with 2 micro/kg intravenous fentanyl, 1.5 mg/kg intravenous propofol, and 0.6 mg/kg intravenous rocuronium, and maintained with desflurane, 2%, and nitrous oxide, 65%, in oxygen [26].
• METHODS: Succinylcholine, the isoquinolines cisatracurium, atracurium, and mivacurium, and the steroids pancuronium, vecuronium, rocuronium, and rapacuronium were tested in human volunteers (n = 6 each) [27].
• CONCLUSION: Phenytoin acutely augments the neuromuscular block produced by rocuronium without altering its plasma concentration or its binding to plasma proteins [28].

Gene context of C07556

• Based on characteristic cis-inhibition patterns of rOCT1-mediated tributylmethylammonium and Oatp2-mediated rocuronium uptake, rOCT1 and Oatp2 could be identified as the organic cation uptake systems1 and 2, respectively, in rat liver [29].
• METHODS: Rocuronium (0.01 mg/kg + 2-10 microg x kg-1 x min-1) was administered to maintain train-of-four (TOF) ratios (assessed every 15 s) of approximately 0.5 and 0.8 over a period of more than 5 min [30].
• Diaphragm muscle RING-finger protein-1 (MURF-1) messenger RNA expression, an E3 ligase of the ubiquitin-proteasome pathway, increased after mechanical ventilation (+212%, p < .001 vs. control) and increased further with combination of rocuronium (+320%, p < .001 vs. control) [10].
• The studies were performed with model compounds tri-n-butylmethylammonium (TBuMA) (a relatively small type 1 organic cation), rocuronium (Roc) (a bulky type 2 organic cation) and the classical P-gp substrate doxorubicin (Dox) [31].
• In liver tissue obtained from four patients undergoing hemihepatectomy, the estimated amount of rocuronium at 2-5 h after administration ranged between 6.3 and 13.2% (n = 4) [32].

Analytical, diagnostic and therapeutic context of C07556

• The pharmacokinetic-pharmacodynamic relationship of rocuronium at the laryngeal adductor muscles and the adductor pollicis was determined in eight patients during general anesthesia [7].
• Its main advantage is the rapid onset of neuromuscular block whereby good or excellent intubating conditions are achieved within 60 to 90 seconds after rocuronium 0.6 mg/kg (2 x ED95), and within 60 to 180 seconds after smaller doses (1 to 1.5 x ED95) [33].
• METHODS: Twenty patients undergoing liver transplantation were given rocuronium, 600 microg/kg, after induction of anesthesia and again after perfusion of the transplanted liver [5].
• INTERVENTIONS: Rats were divided into four groups: a control group, a group of anesthetized rats breathing spontaneously for 24 hrs, and two groups submitted to mechanical ventilation for 24 hrs, receiving a continuous infusion of either 0.9% NaCl or rocuronium [10].
• Arterial blood was sampled during onset and offset of effect, and the plasma concentration of rocuronium was measured with high-performance liquid chromatography [4].

References