Factors Affecting the Pharmacokinetic Characteristics of Rapacuronium.
Fisher, Dennis M. MD; Kahwaji, Raymond MD; Bevan, David MB; Bikhazi, George MD; Fragen, Robert J. MD; Angst, Martin S. MD; Ornstein, Eugene MD, PhD; Matteo, Richard S. MD
90(4):993-1000, April 1999.
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Background: Rapacuronium 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.
Methods: Of 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.
Results: Rapacuronium'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.
Conclusions: In 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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