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Factors Affecting the Pharmacokinetic Characteristics of Rapacuronium

 

作者: Dennis Fisher,   Raymond Kahwaji,   David Bevan,   George Bikhazi,   Robert Fragen,   Martin Angst,   Eugene Ornstein,   Richard Matteo,  

 

期刊: Anesthesiology  (OVID Available online 1999)
卷期: Volume 90, issue 4  

页码: 993-1000

 

ISSN:0003-3022

 

年代: 1999

 

出版商: OVID

 

关键词: Modeling;muscle relaxants;ORG9487;population analysis.

 

数据来源: OVID

 

摘要:

BackgroundRapacuronium is a new nondepolarizing muscle relaxant with rapid onset and offset. As part of a study to determine its neuromuscular effects, the authors sampled plasma sparsely to determine the influence of age, gender, and other covariates on its pharmacokinetic characteristics.MethodsOf 181 patients receiving a single bolus dose of 0.5‐2.5 mg/kg rapacuronium, 43 (aged 24‐83 yr) had plasma sampled 3 or 4 times to determine plasma concentrations of rapacuronium and its metabolite, ORG9488. Pharmacokinetic analysis was performed using a population approach (mixed‐effects modeling) to determine the influence of demographic characteristics and preoperative laboratory values on the pharmacokinetic parameters.ResultsRapacuronium's weight‐normalized plasma clearance was 7.03 [middle dot] (1 ‐ 0.0507 [middle dot] (HgB ‐ 13)) ml [middle dot] kg‐1[middle dot] min‐1, where HgB is the patient's preoperative value for hemoglobin (g/100 ml); however, rapacuronium's blood clearance (11.4 +/− 1.4 ml [middle dot] kg‐1[middle dot] min‐1, mean +/− SD) did not vary with hemoglobin. Rapacuronium's weight‐normalized pharmacokinetic parameters were not influenced by age, gender, or other covariates examined. Plasma concentrations of ORG9488 were typically less than 14% those of rapacuronium during the initial 30 min after rapacuronium administration.ConclusionsIn this patient population, neither age nor gender influence elimination of rapacuronium. This finding contrasts to an age‐related decrease in plasma clearance observed in a study of 10 healthy volunteers and in a pooled analysis of the pharmacokinetic data from 206 adults in multiple clinical studies. Even if ORG9488 has a potency similar to that of rapacuronium, its plasma concentrations after a single bolus dose of rapacuronium are sufficiently small to contribute minimally to neuromuscular blockade.

 

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