Plasma levels, protein binding, and elimination data of lidocaine and active metabolites in cardiac patients of various ages

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Abstract
The serum and urine levels of lidocaine and 2 active dealkylated metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), were determined by HPLC [high-performance liquid chromatography] in 33 cardiac patients receiving lidocaine [an antiarrhythmic agent] for more than 1 day. Clinical assessment of nervous system toxicity was carried out at the time of blood drawing. The ratios in serum of MEGX to lidocaine and of GX to lidocaine were 0.36 .+-. 0.26 (mean .+-. SD) and 0.11 .+-. 0.11. Lidocaine and MEGX binding to serum proteins from 7 patients 2 days after their myocardial infarctions were 55.4 .+-. 5.9% and 14.3 .+-. 3.0%. After correction for this difference in protein binding, the MEGX/lidocaine ratio in serum water was 0.68 .+-. 0.49. MEGX levels in serum water were 80% or more of the lidocaine levels in 11 of the 33 patients. GX binding was 5 .+-. 4%. Even after correction for protein-binding differences, GX levels in serum water were low compared to lidocaine levels. The steady-state serum GX concentration normalized for lidocaine infusion rate declined with age. Of 27 patients without toxicity, 6 had serum lidocaine levels above 8 .mu.g/ml. Five of 6 patients with toxicity had levels less than 8 .mu.g/ml. The renal clearance of lidocaine, MEGX and GX was less than creatinine clearance in most patients. MEGX, but not GX, evidently contributes to the pharmacologic activity of lidocaine therapy in a substantial fraction of patients. The concept of a single value for the upper limit of the therapeutic level of lidocaine in serum is apparently an oversimplification because it does not take into account individual differences in drug-protein binding or accumulation of active metabolites.