Hepatic Elimination of Org-Nc45 and Pancuronium

Durant, N. N.; Houwertjes, M. C.; Agoston, S

doi:10.1097/00000542-197909001-00267

Cited by 3 publications

(4 citation statements)

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“…This contrasts with pancuronium, in which the main metabolite (3-hydroxypancuronium), representing approximately 25% of an injected dose, is 50% as potent as the parent drug (36). Biliary excretion of vecuronium in animals and humans accounts for 30-50% of the injected dose (37)(38)(39)(40). This suggests that severe liver disease may prolong the duration of action of vecuronium.…”

Section: Metabolism and Excretionmentioning

confidence: 98%

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Comparison of the Pharmacology of Vecuronium and Atracurium with That of Other Currently Available Muscle Relaxants

Hilgenberg¹

1983

Anesthesia & Analgesia

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The search for new muscle relaxants is an attempt to improve on the undesirable pharmacologic properties of currently available nondepolarizing muscle relaxants. Ideally, new muscle relaxants would exhibit fewer cardiovascular hemodynamic side effects, have fewer cumulative effects, possess rapid onset of and shorter durations of action, and be less dependent on hepatic and/or renal function for metabolism and excretion. Furthermore, drug metabolites should be pharmacologically inactive. Two new nondepolarizing muscle relaxants, vecuronium (Norcuron) and atracurium (BW 33A), are examples of drugs approaching these ideal muscle-relaxant characteristics. Currently, these drugs are used clinically in Europe and are undergoing clinical trials in this country.

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Section: Metabolism and Excretionmentioning

confidence: 98%

“…This suggests that severe liver disease may prolong the duration of action of vecuronium. Indeed, the intensity and duration of action of vecuronium in animals are greater in experiments that exclude hepatic circulation (40). The influence of hepatic disease in humans on vecuro- Figure 7.…”

Section: Metabolism and Excretionmentioning

confidence: 99%

Comparison of the Pharmacology of Vecuronium and Atracurium with That of Other Currently Available Muscle Relaxants

Hilgenberg¹

1983

Anesthesia & Analgesia

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“…However, in their Org NC45 study, the elimination half-life was determined from plasma concentration values apparently collected over 1 h following administration of Org NC45 compared with at least 6h for pancuronium. Durant, Houwertjes and Agoston (1979) found that duration of neuromuscular blockade following Org NC45 was not prolonged by ligation of renal pedicles in cats; the duration of pancuronium block was significantly prolonged. We have compared the pharmacokinetics and neuromuscular blockade of Org NC45 in patients with normal renal function with those with renal failure.…”

mentioning

confidence: 89%

Pharmacokinetics of Org Nc45 (Norcuron) in Patients With and Without Renal Failure

Fahey¹,

Morris²,

Miller³

et al. 1981

British Journal of Anaesthesia

121

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To determine the influence of renal failure on the pharmacokinetics and neuromuscular blockade of Org NC 45 (Norcuron), a new monoquaternary homologue of pancuronium, 13 patients under halothane and nitrous oxide anesthesia were studied. Org NC 45 was administered by 2-min infusion in doses of 0.28 mg kg-1 (normal renal function group, n = 4) and 0.14 mg kg-1 (renal failure group, n = 5). Four additional patients with normal renal function were given Org NC 45 0.14 mg kg-1 to determine the onset, duration and recovery rate of neuromuscular blockade. The serum concentration of Org NC 45 was determined by normal-phase high performance liquid chromatography (sensitivity 50 ng ml-1), and a two-compartment open pharmacokinetic model was fitted to resulting data. Estimates of distribution half-life (T 1/2 alpha), elimination half-life (T 1/2 beta), volume of distribution at steady state (Vss) and clearance of Org NC 45 did not differ significantly between patients with normal renal function and those with renal failure. The onset, duration and recovery rate times of the neuromuscular blockade by Org NC 45 0.14 mg kg-1 in patients with normal renal function and those with renal failure did not differ significantly.

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“…Studies in the cat by Agoston and colleagues (1977) revealed that, after 3min, 9% of the total dose of pancuronium was present in the liver, compared with 41% for Org 6368. The liver is important in the removal of Org NC 45 from the blood stream, since temporary or permanent exclusion of the liver from the circulation has been shown to produce a significant increase in its duration of action (Durant, Houwertjes and Agoston, 1979). Although renal excretion of pancuronium is the main route of elimination in man (Agoston et al, 1973;Buzello, 1975), a considerable prolongation of neuromuscular blockade was reported by Somogyi, Shanks and Triggs (1977) in patients with extrahepatic cholestasis.…”

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confidence: 99%

Bile Salts and Neuromuscular Blocking Agents

Westra

Houwertjes

Wesseling

et al. 1981

British Journal of Anaesthesia

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The influence of the primary bile salts taurocholate and chenodeoxycholate on the neuromuscular blockade of the non-depolarizing drugs Org 6368, pancuronium, Org NC 45 and hexafluorenium was studied in cats. An increase in the effects of these agents, all possessing widely varying molecular structures, was found following administration of the bile salts. The bile salt concentrations in plasma were similar to those obtained after 9-10 days of extrahepatic cholestasis in cats. The effect of Org NC 45, a new monoquaternary analogue of pancuronium, was increased more than that of pancuronium. This increase in effect is probably a result of inhibition of the hepatic uptake of the neuromuscular blocking drugs. The neuromuscular blocking effect of gallamine was not influenced significantly by the administration of bile salts.

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Hepatic Elimination of Org-Nc45 and Pancuronium

Cited by 3 publications

References 0 publications

Comparison of the Pharmacology of Vecuronium and Atracurium with That of Other Currently Available Muscle Relaxants

Comparison of the Pharmacology of Vecuronium and Atracurium with That of Other Currently Available Muscle Relaxants

Pharmacokinetics of Org Nc45 (Norcuron) in Patients With and Without Renal Failure

Bile Salts and Neuromuscular Blocking Agents

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