title: 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.
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
authors.forename: L Y
authors.initials: LY
authors.lastname: Ngo
authors.forename: Y K
authors.initials: YK
authors.lastname: Tam
authors.forename: S
authors.initials: S
authors.lastname: Tawfik
authors.forename: R T
authors.initials: RT
authors.lastname: Coutts
authors.forename: M R
authors.initials: MR
authors.lastname: Gray
mesh_terms: D000818:Animals; D019540:Area Under Curve; D004285:Dogs; D005260:Female; D007262:Infusions, Intravenous; D008012:Lidocaine / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D008099:Liver / Q000098:blood supply / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects
chemical_list: D008012:Lidocaine