LIDOCAINE PHARMACOKINETICS AND TOXICITY IN NEWBORN PIGS

In newborn infants suffering from perinatal asphyxia seizures, lidocai ne (LD) has proved to be an effective anticonvulsant. At high concentr ations, however, LD can itself cause convulsions. The convulsive conce ntration of LD (LDconv) varies among species. The aim of this study wa s to describe LD pharmacokinetics and to define the LDconv in awake ne wborn pigs. Eighteen Land race newborn pigs aged 12-60 h, weight 1.0-2 .5 kg, were enrolled. LD, 2 mg/kg intravenous (IV) bolus, (n = 11) was given to estimate pharmacokinetic variables. Continuous LD infusion 2 mg.kg(-1).min(-1) IV (n = 5) and repeated bolus doses of 15 mg/kg (n = 4) were given until electroencephalogram-confirmed seizures appeared . After the bolus injection, the elimination half-life for LD was 0.87 -5.44 h. Increasing plasma concentration (LDpl) during infusion result ed in sedation after 5-10 min and in shivering, nystagmus, neck extens ion, tonic-clonic seizures at LDconv of 40.6 +/- 12.7 mg/L (mean +/- S D). The unbound LDpl at seizures was 4.4 +/- 2.4 mg/L. Younger animals convulsed at higher LDconv (r(2) = 0.85). LD pharmacokinetics in newb orn pigs were found to be dose-dependent at high plasma concentrations . At lower plasma concentrations, LD pharmacokinetics appeared to be l inear. The central nervous system is the primary target for the toxic effect of LD in awake newborn pigs. LD neurotoxicity is age-dependent, and younger Figs convulse at a higher LDconv.