tabolites and unchanged drug are excreted by the kidneys. biotransformation includes oxidative n-dealkylation, ring hydroxylation, cleavage of the amide linkage, and conjungation. n-dealkylation, a major pathway of biotransformation, yields the metabolites monoethylglycinexylidide and glycinexlidide. the pharmacological/toxicological actions of these metabolites are similar to, but less potent than, those of lidocaine. approximately 90% of lidocaine administered is excreted in the form of various metabolites and less than 10% is excreted unchanged. the primary metabolite in urine is a conjugate of 4-hydroxy-2, 6-dimethylaniline. the plasma binding of lidocaine is dependent on drug concentration and the fraction bound decreases with increasing concentration. at concentration of 1 to 4 g of free base per ml, 60 to 80 percent of lidocaine is protein bound. binding is also dependent on the plasma concentration of the alpha-1-acid-glycoprotein. lidocaine crosses the blood-brain and placental barriers, presumably by passive diffusion. studies of lidocaine metabolism following intravenous bolus injections have shown that the elimination half-life of this agent is typically 1.5 to 2 hours. because of the rapid rate at which lidocaine is metabolized, any condition that affects liver function may alter lidocaine kinetics. the half-life may be prolonged two-fold or more in patients with liver dysfunction. renal dysfunction does not affect lidocaine kinetics but may increase the accumulation of metabolites. factors such as acidosis and the use of cns stimulants and depressants affect the cns levels of lidocaine required to produce overt systemic effects. objective adverse manifestations become increasingly apparent with increasing venous plasma levels above 6 g free base per ml. in the rhesus monkey, arterial blood levels of 18-21 g/ml have been shown to be threshold for convulsive activity.