Pharmacokinetics and Pharmacokinetic-Dynamic Relationship Between Rapacuronium (Org 9487) and Its 3-Desacetyl Metabolite (Org 9488)

A pharmacokinetic-dynamic explanation of the rapid onset–offset of rapacuronium

“…Factors contributing to the rapid onset of rapacuronium PK-PD modelling has shown that the rate constant of transport between plasma and effect compartment, the k e0 , for rapacuronium is 0.4-0.45 min À1 [3,4], corresponding to an equilibration half-life of 1.6 min. This value of k e0 is markedly higher for rapacuronium than for any of the currently available neuromuscular blocking agents (Fig.…”

“…The doses have been adjusted to achieve a plasma concentration of 10 mg L À1 at 1 min after a bolus administration. The plasma concentration profiles have been calculated from mean pharmacokinetic data of rapacuronium [4] and rocuronium (unpublished data), obtained after an infusion over 2-6 min.…”

Performance of an Iterative Two-Stage Bayesian Technique for Population Pharmacokinetic Analysis of Rich Data Sets

“…Data were taken from a clinical PK-PD modeling study of rapacuronium performed in our department (13). In short, ten patients (eight male, two female; aged 26Y64 years; body weight 62Y88 kg; ASA class IYIII), undergoing elective surgery, received thiopental-fentanyl-isoflurane-O 2 -N 2 O anesthesia.…”

“…The study design and population model were close to that of the clinical study (13). In the simulation study, a dose of 1 mg kg j1 was administered to a panel of ten subjects (body weight 70 kg) by an intravenous infusion over 4 min.…”

Muscle relaxants in paediatric day case surgery

“…Rapacuronium, is a monoquaternary aminosteroidal muscle relaxant characterized by a rapid onset and a short duration of action, suggesting a possible use in paediatric day case surgery [30]. It is metabolized in the liver primarily to a 3-hydroxy metabolite (Org 9488), which itself is a neuromuscular blocking drug, having twice the potency of rapacuronium (biophase EC 50 0.4 Â rapacuronium) and an intermediate to long duration of action [31]. Excretion of rapacuronium and its metabolites is organ dependent and there is some evidence of cumulation of Org 9488 after repeated doses or an infusion [32].…”