CLINICAL-PHARMACOLOGY OF ROCURONIUM (ORG-9426) - STUDY OF THE TIME-COURSE OF ACTION, DOSE REQUIREMENT, REVERSIBILITY, AND PHARMACOKINETICS

Study Objective: To evaluate the time course of action, dose requirement, reversibility, and pharmacokinetics of rocuronium (Org 9426) under 3 anesthetic techniques (nitrous oxide-fentanyl supplemented with propofol halothane, or isoflurane). Design: Prospective, randomized study. Setting: Operating suite at a university hospital. Patients: 36 ASA physical status I-III patients aged 18 to 65 years who were scheduled for elective surgery. Interventions: The time course of action of an intubation, close of rocuronium 600 mu g/kg was investigated in 36 patients. In 18 of these patients, the maintenance dose requirement of rocuronium and reversibility by neostigmine were evaluated. In the remaining 18 patients, the pharmacokinetics of rocuronium rocuronium after the intubating dose were studied. Neuromuscular transmission was monitored by mechanomyography. Venous blood samples and urine were analyzed by high-performance liquid chromatography. Measurements and Main Results: With the exception of a longer clinical duration of rocuronium-induced neuromuscular block in the isoflurane group compared with the propofol group (p = 0.03), time course of action variables were similar in the 3 groups. In patients receiving maintenance doses of rocuronium, the dose requirement until reversal was 636 +/- 191 mu/g/kg/hr, 496 +/- 107 mu g/kg/hr, and 384 +/- 127 mu g/kg/hr for the propofol halothane, and isoflurane groups, respectively (p = 0.02 for the isoflurane group vs. the propofol group). With respect to the reversal of a rocuronium-induced neuromuscular block, there were no differences in the percentage recovery or rate of recovery among the 3 groups. Pharmacokinetic analysis showed no significant differences for rocuronium during the 3 anesthetic techniques. Conclusion: Isoflurane potentiates the rocuronium-induced neuromuscular block resulting in a longer clinical duration and lower maintenance dose requirement. This difference is not explained by differences in pharmacokinetics but is probably due to increased sensitivity of the neuromuscular junction to rocuronium during isoflurane anesthesia