Effect of the duration of infusion on the disposition of lidocaine in dogs.

Lidocaine is a commonly used and efficacious antiarrhythmic agent whose pharmacokinetics after a rapid intravenous bolus injection have been extensively studied. Due to its short half-life, a continuous infusion of lidocaine is necessary whenever therapeutic blood levels need to be maintained for prolonged periods of time. Recent work in man has shown that the elimination of lidocaine is much slower after a prolonged infusion than after a bolus. We present the results of a pharmacokinetic study of the disposition of lidocaine after the discontinuation of short (90 minutes) and long (24 hours) intravenous infusions which demonstrate that in both cases the elimination of lidocaine is best explained by a two-compartment open model with elimination from the central compartment and that the longer half-life of lidocaine after a prolonged infusion is due to an impairment of its hepatic extraction. Lidocaine hepatic elimination data obtained at the end of short- and long-term infusions confirmed the inferences drawn from the pharmacokinetic analysis by demonstrating that a long-term infusion produces an important decrease in the arterial clearance and hepatic extraction rate of lidocaine.