Pharmacokinetics and Pharmacodynamics of Vercuronuium in Patients With Cholestasis

Lebrault, C.; Duvaldestin, P.; Henzel, D.; Chauvin, M.; Guesnon, P

doi:10.1093/bja/58.9.983

Cited by 52 publications

(4 citation statements)

References 11 publications

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“…Consequently, after large or repeated doses, prolongation of both clinical duration and recovery index should be observed in patients with hepatobiliary tract disease. Indeed, both reduced CL (table IV) and dramatically increased durations of neuromuscular effects have been reported after high vecuronium doses (0.2 to 0.3 mg/kg) in patients with cirrhosis (Lebrault et al 1985) and cholestasis (Lebrault et al 1986). In contrast, after lower doses (0.1 mg/kg) alcoholic liver disease had no apparent effect on its pharmacokinetics or duration of action (Arden et al 1988).…”

Section: Vecuroniummentioning

confidence: 94%

Clinical Pharmacokinetics of Neuromuscular Blocking Drugs

Ágoston

Vandenbrom

Wierda

1992

Clinical Pharmacokinetics

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Neuromuscular blocking agents provide muscle relaxation for a great variety of surgical procedures with light planes of general anaesthesia. Besides having a significant impact in the development of anaesthesia and surgery, these agents continue to play an important role as pharmacological tools in the elucidation of the physiological and pharmacological regulation of neuromuscular transmission and the morphofunctional organisation of the neuromuscular junction. In the daily practice of anaesthesia, muscle relaxants are considered to be safe drugs with predictable, straightforward pharmacological actions. However, the use of relaxants constitutes a deliberate encroachment on respiration, one of the most important physiological mechanisms. The pharmacokinetic behaviour of this class of agents is little influenced by age or anaesthetic agents; however, hepatic or renal disease may profoundly alter their excretion pattern, resulting in prolonged duration of neuromuscular blockade. Biotransformation plays an important role in the total elimination of recently introduced compounds. Consequently, knowledge of the disposition pharmacokinetics, excretion and biotransformation of this class of drugs is indispensable for their rational choice for various surgical procedures. In this review, the known pharmacokinetics of standard compounds (introduced before 1980) are briefly summarised and new information generated by the development of vecuronium, rocuronium, pipecuronium (steroidal agents) and atracurium, mivacurium, doxacurium (benzylisoquinolinium esters) is discussed in more detail.

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Section: Vecuroniummentioning

confidence: 94%

Clinical Pharmacokinetics of Neuromuscular Blocking Drugs

Ágoston

Vandenbrom

Wierda

1992

Clinical Pharmacokinetics

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“…251 Vecuronium is in large part (~80%) removed by hepatic metabolism and biliary excretion and therefore is a less than ideal choice for patients with liver disease. [252][253][254] Because the kidney also plays a role in clearing vecuronium (and all the aminosteroid compounds), renal dysfunction prolongs vecuronium's effects. [255][256][257][258] Unfortunately the cost of acquiring vecuronium is approximately 15 times that of an equivalent paralyzing dose of pancuronium.…”

Section: Vecuroniummentioning

confidence: 99%

Analgesia, Sedation, and Therapeutic Paralysis in the Critically Ill

Wheeler¹

1997

Semin Respir Crit Care Med

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“…In pharmacokinetic studies of vecuronium, the first sample was drawn 1 min Lien et al 1991;Meiste1man et al 1986;), 2 min (Arden et al 1988;Lynam et al 1988), 4 min (Fahey et al 1981; Van der Veen & Bencini 1980) or even 5 min (Lebrault et al 1985(Lebrault et al , 1986 after bolus administration. This paucity of data points over the first 5 min and the lack of pharmacokinetic data during the first minute may lead to inaccurate extrapolations.…”

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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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Pharmacokinetics and Pharmacodynamics of Vercuronuium in Patients With Cholestasis

Cited by 52 publications

References 11 publications

Clinical Pharmacokinetics of Neuromuscular Blocking Drugs

Clinical Pharmacokinetics of Neuromuscular Blocking Drugs

Analgesia, Sedation, and Therapeutic Paralysis in the Critically Ill

Importance of Early Blood Sampling on Vecuronium Pharmacokinetic and Pharmacodynamic Parameters

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