Disposition and Urinary Excretion of Vecuronium Bromide in Anesthetized Patients with Normal Renal Function or Renal Failure

Bencini, A; Scaf, A. H. J.; Sohn, Young-Jong; Meistelman, Claude; Lienhart, A.; Kersten, U.; Schwarz, Sebastian; Ágoston, S.

doi:10.1213/00000539-198603000-00005

Cited by 87 publications

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“…Furthermore, most studies involved the measurement of peripheral venous concentrations (Arden et al 1988;Bencini et al 1986;Cronnely et al 1983;Fahey et al 1981;LebrauIt et al 1985LebrauIt et al , 1986Lynam et al 1988;Meistelman et al 1986;Rupp et al 1987;Sohn et al 1986; Van der Veen & Bencini 1980) which can be markedly lower than arterial concentrations (Chiou 1989;Donati et al 1991b). Since vecuronium block develops over 3 min, the first samples drawn 1 to 5 min after injection were obtained while block was well initiated, or even when it was complete.…”

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confidence: 99%

Importance of Early Blood Sampling on Vecuronium Pharmacokinetic and Pharmacodynamic Parameters

Ducharme

Bevan

Donati

1993

Clinical Pharmacokinetics

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The effect of early blood sampling on the description of the vecuronium pharmacokinetic-pharmacodynamic relationship was studied following a bolus injection. Sample collection every 10 sec during the first 2 min showed a high concentration peak at 30 to 40 sec, accounting for an important proportion of the total area under the plasma concentration-time curve (AUC). Neglecting it, using only blood samples drawn at 1 and 2 min (limited sampling), led to a significant overestimation of noncompartmentally derived values of mean residence time, clearance, volume of distribution at steady-state and rate of transfer of vecuronium into the effect compartment. Compartmental pharmacokinetics could not be applied to concentration-time curves constructed with early samples, but limited sampling data were fitted to a 2-compartment model. Derived compartmental pharmacokinetic and pharmacokinetic-pharmacodynamic parameters were similar to those obtained noncompartmentally with complete sampling every 10 sec, because back-extrapolation to time zero contributed to the increase in the AUC. However, compartmental analysis does not provide an accurate description of concentration changes following injection.

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confidence: 99%

Importance of Early Blood Sampling on Vecuronium Pharmacokinetic and Pharmacodynamic Parameters

Ducharme

Bevan

Donati

1993

Clinical Pharmacokinetics

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“…Similar results have been obtained for cumulativeand single-dose techniques for the longer acting muscle relaxants d-tubocurarine and pancuronium.5 However, for atracurium and vecuronium, cumulative-dose techniques tend to require higher doses to produce equivalent blockade, most likely because of the relatively rapid elimination and redistribution of these drugs during administration of incremental doses.3'" Although both drugs have intermediate (30 to 45 minutes) durations of action, atracurium's effect is terminated by Hofmann elimination and nonspecific ester hydrolysis,'" whereas that of vecuronium's is by hepatic metabolism and renal excretion. [12][13][14] It follows that cumulative dose-response techniques could be used accurately for drugs with short to intermediate durations of action if the interval between the first and last dose is reduced or if the amount of drug lost by elimination or distribution during the study period is replaced. Thus it is expected that the administration of an infusion to replace eliminated or redistributed drug would tend to improve the accuracy of cumulative-dose techniques, defined as the ability to generate dose-response curves that are not different from the traditional single-dose method.…”

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confidence: 99%

Cumulative dose-response with infusion: a technique to determine neuromuscular blocking potency of atracurium and vecuronium

Smith

Donati

Bevan

1988

Clin Pharmacol Ther

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The ability of cumulative dose-response techniques to obtain accurate data is most likely limited by redistribution and elimination of the drug during the study period. Therefore the usefulness of these techniques would be improved by replacing the amount of drug lost. This hypothesis was assessed for the intermediate-duration neuromuscular blockers vecuronium and atracurium, and calculations were made based on a pharmacokinetic model with an effect compartment. Sixty patients received either single doses (SD) (n = 36), cumulative doses (CD) (n = 12), or CD of vecuronium or atracurium with an infusion (CDI) to replace eliminated or redistributed drug (n = 12). The force of contraction of the adductor pollicis muscle in response to train-of-four stimulation was measured and recorded. Linear regressions were obtained between the logit transformation of neuromuscular blockade at the adductor pollicis and log dose. The potencies obtained with all three methods were within 20% of each other. For vecuronium the ED90 was (mean +/- SE) 0.034 +/- 0.002 (SD), 0.037 +/- 0.003 (CD), and 0.036 +/- 0.003 mg/kg (CDI). For atracurium the ED90 was 0.175 +/- 0.009 (SD), 0.206 +/- 0.019 (CD), and 0.179 +/- 0.015 mg/kg (CDI). Calculated values corresponded well with measured values. The calculations predicted that the agreement between single- and cumulative-dose techniques would be improved if (1) the dose increment was increased, (2) the elimination half-life was increased above 20 minutes, or (3) an infusion was added.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…This characteristic can be explained by a plasma clearance of vecuronium double that of pancuronium. In a subsequent pharmacokinetic study, however Bencini et al (1986a), using a more sensitive fluorimetric method, observed slight prolongation of the elimination half-life from 2 h in controls to 2.5 h in patients with renal failure. Using a high-pressure liquid chromatographic method of measurement of the plasma drug concentration, they showed the parmacokinetics of vecuronium to be unaltered in patients with renal failure.…”

Section: Vecuroniummentioning

confidence: 89%

Muscle Relaxants

1995

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Originally published by Springer-Verlag Tokyo in 1995. Softcover reprint ofthe hardcover lst edition 1995 This work is subject to copyright. AII rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of iIIustrations, recitation, broadcasting, reproduction on microfilms or in other ways, and st<;>rage in data banks. The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product Iiability: The publisher can give no guarantee for information about drug dosage and application thereof contained in this book. In every individual case the respective user must check its accuracy by consulting other pharmaceuticalliterature. PrefaceThe Fifth International Neuromuscular Meeting was held in Tokyo from November 17 through 20, 1994, and it was my privilege to chair these proceedings. It might seem to some that everything that can be said about the pharmacology of neuromuscular blocking agents (NBA) and their antagonists, the clinical use of NBAs, and the anatomy and physiology of neuromuscular receptor sites has already been said. From the beginning of the meeting, it became clear, not surprisingly, that such is not the case.It was a tortuous path from the first recorded clinical use of a curariform substance by Lawen in 1912 to the introduction of Intocostrin by Griffith in Canada, as reported in a 1942 issue of Anesthesiology. The practice of anesthesiology and surgery was changed forever. It was to be many years before a clear understanding of the neuromuscular junction (NMJ) and receptor pharmacology emerged. Prejunctional and post junctional actions of NBAs can now be differentiated and these data are clearly presented in these proceedings. The effects of catecholamine stress, burns, immobilization, and endotoxicosis as well as those from chronic infusions of curare and succinylcholine on NMJ pertubations have been elucidated. Recent studies utilizing the tools of molecular biology have helped to explain both prolonged blockade and sudden, lethal hyperkalemia following the administration of succinylcholine.Special considerations are addressed for administering NBAs to children, the elderly, and those with impaired renal and hepatic function. The relationship between the pharmacokinetics of d-Tubocurarine (dTc) , vecuronium, and atracurium and the volume of distribution in children is discussed, as is the decreased prejunctional acetylcholine stores in neonates and infants. In the elderly, elimination of NBAs (except for atracurium and, possibly, pipecuronium) is delayed due to decreased plasma clearance. In this respect, atracurium is unique since its half-life is independent of either renal or hepatic function. Elimination pathways of the new steroidal NBAs have not been established. The reader will be reminded, however, that the influence of hepatic disease ...

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Disposition and Urinary Excretion of Vecuronium Bromide in Anesthetized Patients with Normal Renal Function or Renal Failure

Cited by 87 publications

References 0 publications

Importance of Early Blood Sampling on Vecuronium Pharmacokinetic and Pharmacodynamic Parameters

Importance of Early Blood Sampling on Vecuronium Pharmacokinetic and Pharmacodynamic Parameters

Cumulative dose-response with infusion: a technique to determine neuromuscular blocking potency of atracurium and vecuronium

Muscle Relaxants

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