Serum lidocaine concentrations following application to the oropharynx: effects of cimetidine

Solutions of lidocaine hydrochloride are widely used for anesthesia of the oropharynx and respiratory tract prior to endoscopic procedures. It is commonly believed that this route of administration is not associated with clinically significant systemic absorption of the drug, and large doses of topical lidocaine are routinely used in this setting. Serious adverse effects, including seizures, occasionally occur. The extent of absorption of lidocaine from the oropharynx was studied in eight healthy volunteers. Wide variation in serum lidocaine concentrations was observed. A 14-fold range of peak lidocaine concentrations occurred following identical, accurately metered doses of a lidocaine aerosol spray preparation. The effects of cimetidine on lidocaine pharmacokinetics were also studied. Therapeutic doses of oral cimetidine significantly increased the area under the lidocaine time-concentration curve (p = 0.019), but no effect on the terminal-phase elimination rate constant was observed. Serum concentrations of alpha 1-acid glycoprotein, a major binding protein of lidocaine, were significantly elevated following cimetidine (p = 0.030). Maximum lidocaine concentration, time to reach maximum concentration, and mean residence time of lidocaine were unchanged following cimetidine. These observations suggest an effect of cimetidine on the volume of distribution of lidocaine. Because of the wide variability in lidocaine pharmacokinetics and the potentially serious nature of adverse reactions, caution is advised in the use of topical lidocaine solutions in "standard" doses.