In vivo pharmacodynamic interaction between pipecuronium and certain H2 blockers

Abstract

Objective: To investigate the pharmacodynamic interaction of H2-receptor antagonists (i.e., famotidine and roxatidine acetate) with a neuromuscular blocker, pipecuronium using sciatic nerve stimulated gastrocnemius preparation of rats in vivo . Materials and Methods: The dose-response curve of pipecuronium (10-50 mg/kg i.v.) was elicited and the dose (ID50; 26.89 mg/kg i.v.) required to cause 50% of blockade of basal contractile twitch response was calculated. Benzyl alcohol (0.9 % v/v), famotidine (0.5, 2.0, 5.0 mg/kg i.v.) or roxatidine acetate (0.05, 0.2, 0.5 mg/kg i.v.) were administered 30 min prior to pipecuronium administration and their effects were studied on the dose-response curve of pipecuronium. Results: Famotidine did not alter the basal contractile twitch responses but with a dose of 2 mg/kg it significantly decreased, while with 5 mg/kg, it significantly increased the ID50 of pipecuronium. At higher dose (5.0 mg/kg) it significantly increased the time required for the onset of blockade without affecting the other parameters. Roxatidine acetate (0.2, 0.5 mg/kg) by itself produced significant neuromuscular blockade but did not alter the ID50 of pipecuronium, while with higher dose (0.5 mg/kg) it significantly decreased the same. Roxatidine (0.05 and 0.2 mg/kg) significantly increased the time required for onset of pipecuronium-induced neuromuscular blockade. At varying doses roxatidine also significantly increased the time required for peak effect and the recovery from the paralysis. Conclusion: Compared to roxatidine, famotidine produced less pharmacodynamic drug interaction with pipecuronium in rats. Such an interaction should be explored in clinical practice.