Influence of renal failure on the pharmacokinetics and neuromuscular effects of a single dose of rapacuronium bromide

Background: Because renal function affects the elimination of muscle relaxa nts, each new muscle relaxant must be evaluated in patients with renal fail ure. Accordingly, the neuromuscular effects and pharmacokinetics of rapacur onium were identified in patients with renal failure. Methods: Rapacuronium (1.5 mg/kg) was administered to 10 healthy volunteers and 10 patients with renal failure who were undergoing non-transplant surg ery, were 18-45 yr old, and were anesthetized with propofol, The adductor p ollicis muscle twitch tension was monitored. Plasma samples were obtained f requently for a period of 8 h to measure the concentrations of ORG9487 and its metabolite, ORG9488, Pharmacokinetic parameters were determined using m ixed-effects modeling. Results: One patient was excluded from analysis because he was taking pheny toin chronically. Twitch depression at 1 min was less in patients than in h ealthy volunteers (median values: 92% in patients, 99% in volunteers). The times to 90% and peak twitch depression; to 10%, 25%, and 75% twitch recove ry; and to 70% and 80% train-of-four ratios mere similar in volunteers and patients. Rapacuronium's clearance was 32% less in patients with renal fail ure; in both groups, clearance decreased 0.909% per year of age compared wi th the value in a 30 yr old. The steady state distribution volume was 14% l ess in women than in men and 16% less in patients than in volunteers. For O RG9488, clearance was 85% less in patients than in volunteers. Conclusions: The neuromuscular effects of a single dose of rapacuronium are affected minimally by renal failure. However, the decreased clearance of r apacuronium and its potent metabolite in renal failure suggests that repeat ed dosing of rapacuronium may lead to prolonged effects in patients with re nal failure.