Beeinflussung der Pharmakodynamik von Rocuronium durch Cimetidin

Cimetidine is a commonly used H₂-receptor antagonist that has been recommended for the prevention of acid aspiration syndrome and has been shown to potentiate vecuronium-induced neuromuscular block. The present study was designed to investigate the influence of a single IV dose of cimetidine on the neuromuscular effects of rocuronium, an analogue of vecuronium with a short onset time. Methods. Twenty adults aged 18–65 years were included in the study with their informed consent and approval of the Ethics Committee. Following oxazepam premedication, 10 patients were randomly allocated to receive cimetidine 400 mg IV 30 min before anaesthesia. After fentanyl and thiopentone induction, single-twitch stimulation of the ulnar nerve was performed every 10 s. Following stabilisation of control responses, patients received rocuronium 0.6 mg/kg for intubation. Anaesthesia was maintained with enflurane ≤0.8 vol.% (end-tidal) and 65% nitrous oxide. Onset time and recovery times to 25% and 75% of the twitch control values were recorded. Results. Onset and recovery times did not differ between groups. Conclusions. The results of the present study demonstrate that cimetidine does not increase the duration of rocuronium neuromuscular blockade. Inhibition of the cytochrome P450 system or a direct effect at the neuromuscular junction have been suggested as the mechanisms of drug interaction associated with cimetidine. Impairment of hepatic microsomal drug metabolism results in a prolonged duration of action of vecuronium, which appears to be eliminated primarily via the liver. Data on the elimination pathway of rocuronium in humans are not available. The fact that cimetidine does not alter the recovery from rocuronium-induced neuromuscular block confirms a previous suggestion that rocuronium may not be eliminated principally by the liver. A direct effect of cimetidine on the neuromuscular junction could not be confirmed by this study. Therefore, cimetidine can be given as premedication without a risk of prolonged rocuronium block.