ABSTRACT
Background: Lignocaine is a local anaesthetic agent that isalso effectively in the acute intravenous treatment of ventriculararrhythmias. The aim of this study was to evaluate the effect oferythromycin, as a prototypical CYP3A4 inhibitor, on thedisposition kinetics of lignocaine in healthy volunteers andpatients with liver cirrhosis.Materials & Methods: A double-blind, randomized controlstudy, thirty male subjects (10 healthy volunteers and 20patients with biopsy-proven liver cirrhosis) participated in thestudy, after giving their informed written consent. The studydesign was approved by the Institutional Ethics Committee.Patients were excluded from this study if they had a history ofgastrointestinal bleeding, severe encephalopathy or any otherdisease. None of the participants was a smoker or a heavyconsumer of alcohol. They were requested to abstain fromalcohol during the preceding week and throughout the period ofinvestigation.Results: In our study showed that there were no statisticallysignificant differences between the three groups for age,weight, height, or body mass index. Our study indicates thatonly in decompensated (Child’s class C) cirrhotic patients werethe disposition kinetics of lignocaine profoundly alteredcompared with healthy volunteers. In particular, CL wasapproximately halved, whereas Vss was increased and,consequently, t1/2 was more than doubled.Conclusion: This study has shown that concomitantadministration of erythromycin causes a moderate butstatistically significant decrease in lignocaine clearance that,contrary to predictions, is quantitatively similar in healthysubjects and cirrhotic patients. Because, erythromycin alsosignificantly increases the AUC of MEGX, which has beenshown to have 80–90% of the antiarrhythmic potency oflignocaine.Keyw