Effects of Intravenous Infusion of Lidocaine on Its Pharmacokinetics in Conscious Instrumented Dogs

Abstract

In this study, potential alterations in hepatic blood flow, plasma protein binding, hepatic tissue binding, and enzyme activities induced by LD iv infusion of lidocaine (LD) were evaluated using a chronically instrumented dog model. Four conscious female mongrel dogs (19.0-23.5 kg) were each given, on days 1 and 10, a 5-min infusion of a mixture of unlabeled LD at approximately 2 mg/kg and 14C-labeled LD at approximately 25 microCi and, on day 8, a 12-h constant rate iv infusion of LD (approximately 76 microg/kg/min). During LD infusion, there was a 11-79% increase in total hepatic blood flow, mainly due to a 1.6-9.2-fold increase in hepatic arterial flow. Despite similar blood clearance (27.5 +/- 6.0 mL/min/kg vs 27.5 +/- 3.5 mL/min/kg), volume of distribution at steady state (1.38 +/- 0.08 L/kg vs 1.36 +/- 0.17 L/kg), and free fraction values of LD between days 1 and 10 (p > 0.05), intrinsic clearance values were consistently reduced (1224 +/- 859 mL/ min/kg vs 285 +/- 104 mL/min/kg; p = 0.034). Furthermore, hepatic tissue uptake of LD and/or its metabolites was less on day 10 than on day 1 (39.7 +/- 14.5 micromol vs 30.1 +/- 15.1 micromol; p = 0.072). The extent of N-dealkylation of LD to MEGX was unaltered, whereas sequential biotransformation of MEGX was impaired. Hence, these findings suggested that LD infusion led to a reduction of hepatic intrinsic clearance, although the change was not significant enough to alter its conventional kinetic parameters.

Antinociceptive, cardiopulmonary, and sedative effects of five intravenous infusion rates of lidocaine in conscious dogs

“…The second N‐de‐ethylation step produces GX, which is eliminated more slowly, may potentiate lidocaine‐induced seizures and lacks anti‐arrhythmic activity. The plasma concentrations of GX start accumulating after 4 hours at an infusion rate of 76 μg kg −1 minute −1 in conscious dogs, while lidocaine and MEGX do not appear to accumulate (Ngo Ly et al. 1997).…”

“…Emesis was observed at plasma lidocaine concentrations greater than 4 μg mL −1 in our study. Nausea and emesis have been reported in conscious dogs receiving 76 μg kg −1 minute −1 for 12 hours (Ngo Ly et al. 1997).…”

“…2006), lidocaine infusions have not yet been examined for antinociceptive effects when administered to conscious dogs. The effects of long‐term lidocaine infusions have only been sparsely reported in dogs, although long‐term lidocaine infusions are popular for promotility in the horse (Ngo et al. 1997; Navas de Solìs & McKenzie 2007).…”

Pharmacokinetics of Lidocaine Hydrochloride Administered with or without Adrenaline for the Paravertebral Brachial Plexus Block in Dogs

“…This precluded the estimation of the disposition pharmacokinetic parameters CL and V, of its terminal elimination rate, and of the absolute bioavailability F. But using one or more i.v. study arms in the same dogs may decrease the intrinsic clearance of lidocaine [35], and therefore hinder the elucidation of the effects of adrenaline on its absorption kinetics. Still, the disposition pharmacokinetic parameters estimated in this study are comparable to those of previous studies: one reported a CL of 0.04 L·min -1 ·kg -1 and a V of 1.44 L·kg -1 after a lidocaine i.v.…”

Pharmacokinetics of lidocaine after intravenous administration to cows

“…, 1996; Orszulak‐Michalak et al. , 2002), dogs (Difazio & Brown, 1972; Ngo et al. , 1997), sheep (Mather et al.…”