Effect of acute and chronic moderate hypoxia on the kinetics of lidocaine and its metabolites and on regional blood flow

Abstract

The effect of acute and chronic hypoxia on the disposition of lidocaine and its metabolites, and on regional blood flow has been examined in conscious beagles (n = 5). Each dog received an infusion of lidocaine for 5 h under three experimental conditions: (1) breathing air; (2) following acute exposure to a FIO 2 of 8% and a FICO 2 of 3.5% to generate a PaO 2 of 45 mmHg without hypocapnia; and (3) after 6 days of hypoxemia. Multiple blood samples were drawn to assess the kinetics of lidocaine and its metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX). Three hours after the end of the infusion of lidocaine, the dogs received radioactive microspheres to estimate hepatic, renal and brain blood flow. Neither acute nor chronic moderate hypoxia affected the kinetics of lidocaine, the parent compound. However, both experimental conditions increased plasma concentrations of MEGX and GX and increased the ratio of the area under their plasma concentration curves to the dose of lidocaine received. Acute moderate hypoxia increased brain blood flow, although it did not affect liver or renal perfusion. Chronic moderate hypoxia did not significantly change the blood flow to any of the organs studied. It was concluded that acute and chronic moderate hypoxia decreases the rate of elimination of both active metabolites of lidocaine without modifying the perfusion to the organs responsible for their elimination.