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 effect s, the authors sampled plasma sparsely to determine the influence of age, g ender, and other covariates on its pharmacokinetic characteristics. Methods: Of 181 patients receiving a single bolus dose of 0.5-2.5 mg/kg rap acuronium, 43 (aged 24-83 yr) had plasma sampled 3 or 4 times to determine plasma concentrations of rapacuronium and its metabolite, ORG9488. Pharmaco kinetic analysis was performed using a population approach (mixed-effects m odeling) to determine the influence of demographic characteristics and preo perative laboratory values on the pharmacokinetic parameters. Results: Rapacuronium's weight-normalized plasma clearance was 7.03 . (1 - 0.0507 . (HgB - 13)) ml . kg(-1) . min(-1), where HgB is the patient's preo perative value for hemoglobin (g/100 mi); however, rapacuronium's blood cle arance (11.4 +/- 1.4 mi . kg(-1) . min(-1), mean +/- SD) did not vary with hemoglobin. Rapacuronium's weight-normalized pharmacokinetic parameters wer e not influenced by age, gender, or other covariates examined Plasma concen trations of ORG9488 were typically less than 14% those of rapacuronium duri ng the initial 30 min after rapacuronium administration. Conclusions: In this patient population, neither age nor gender influence e limination of rapacuronium. This finding contrasts to an age-related decrea se 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 c linical studies. Even if ORG9488 has a potency similar to that of rapacuron ium, its plasma concentrations after a single bolus dose of rapacuronium ar e sufficiently small to contribute minimally to neuromuscular blockade.