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 requireme nt, reversibility, and pharmacokinetics of rocuronium (Org 9426) under 3 anesthetic techniques (nitrous oxide-fentanyl supplemented with pro pofol 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 i ntubation, close of rocuronium 600 mu g/kg was investigated in 36 pati ents. In 18 of these patients, the maintenance dose requirement of roc uronium and reversibility by neostigmine were evaluated. In the remain ing 18 patients, the pharmacokinetics of rocuronium rocuronium after t he intubating dose were studied. Neuromuscular transmission was monito red by mechanomyography. Venous blood samples and urine were analyzed by high-performance liquid chromatography. Measurements and Main Resul ts: With the exception of a longer clinical duration of rocuronium-ind uced neuromuscular block in the isoflurane group compared with the pro pofol group (p = 0.03), time course of action variables were similar i n 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 halotha ne, and isoflurane groups, respectively (p = 0.02 for the isoflurane g roup vs. the propofol group). With respect to the reversal of a rocuro nium-induced neuromuscular block, there were no differences in the per centage recovery or rate of recovery among the 3 groups. Pharmacokinet ic analysis showed no significant differences for rocuronium during th e 3 anesthetic techniques. Conclusion: Isoflurane potentiates the rocu ronium-induced neuromuscular block resulting in a longer clinical dura tion and lower maintenance dose requirement. This difference is not ex plained by differences in pharmacokinetics but is probably due to incr eased sensitivity of the neuromuscular junction to rocuronium during i soflurane anesthesia.