Factors affecting the pharmacokinetic characteristics of rapacuronium.
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 x (1 - 0.0507 x (HgB - 13)) ml x kg(-1) x 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 x kg(-1) x 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.
Fisher
D M
DM
Department of Anesthesia, University of California, San Francisco 94143-0648, USA. fisher@zachary.ucsf.edu
Kahwaji
R
R
Bevan
D
D
Bikhazi
G
G
Fragen
R J
RJ
Angst
M S
MS
Ornstein
E
E
Matteo
R S
RS
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D003473:Neuromuscular Nondepolarizing Agents / Q000493:pharmacokinetics*; D014673:Vecuronium Bromide / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics
D003473:Neuromuscular Nondepolarizing Agents; C117887:Org 9488; D014673:Vecuronium Bromide; C082938:rapacuronium