Pharmacokinetic disposition of lidocaine and its metabolites following a single intravenous dose in healthy and proteinuric dogs

Abstract

The first objective of this study was to establish the time course of lidocaine and its metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), in clinically normal dogs. The ultimate goal was to identify the best time(s) for sample collection when disposition of lidocaine is used as a test of hepatic dysfunction. The second goal was to compare the disposition of lidocaine and its metabolites in normal dogs (G1) and dogs with Alport syndrome, a hereditary proteinuric nephritis (G2). Lidocaine (3 mg/kg) was administered intravenously (IV) to six clinically normal dogs. Blood samples were collected intermittently for twelve hours. Concentrations of lidocaine, MEGX, and GX were quantitated in plasma using high performance liquid chromatography (HPLC). The resulting data was subjected to standard non-compartmental analysis. A concentration plateau for MEGX occurred between 10 and 60 minutes and for GX between 60 and 120 minutes after the administration of lidocaine. The ratio of concentrations of GX to MEGX versus time was linear from 15 minutes to 180 minutes after IV administration of lidocaine characterized by a slope of 0.0144± 0.0090 GX/MEGX ratio over time. Subsequently, lidocaine (3 mg/kg) was administered IV to six dogs with Alport syndrome. Pharmacokinetic parameters for lidocaine, MEGX, and GX were compared between groups using Wilcoxon rank sum test. Values for the parameters did not differ between the two groups (p > 0.05). In G2, the concentration plateaus for MEGX and GX occurred at the same time as that found in G1. However, the concentration plateau for MEGX was greater in G2 (193.5 ng/ml) than G1 (143.6 ng/ml). Also, the concentration plateau for GX was greater in G2 (153.7 ng/ml) than G1 (132.6 ng/ml). The ratio between the concentrations of GX and MEGX versus time was linear in G2 from 15 minutes to 180 minutes after IV administration of lidocaine and was characterized by a slope of 0.0211± 0.0119 GX/MEGX ratio over time. The slopes did not differ statistically between G1 and G2.