REDUCTION OF ORAL BIOAVAILABILITY OF LIGNOCAINE BY INDUCTION OF 1ST PASS METABOLISM IN EPILEPTIC PATIENTS

1. The pharmacokinetics of lignocaine following single oral and intravenous doses have been investigated in six normal volunteers and in six patients receiving chronic antiepileptic drug therapy. 2. After intravenous administration, serum lignocaine levels declined biexponentially in all subjects. The serum clearance (mean +/‐ s.d.) was slightly higher in the patients (0.85 +/‐ 0.09 v 0.77 +/‐ 0.07 l/min) but the difference was not statistically significant. 3. Lignocaine bioavailability after oral administration was more than two‐ fold in the patients than in the normal subjects (0.15 +/‐ 0.06 v 0.37 +/‐ 0.09, P < 0.001). 4. It is suggested that the reduced bioavailability of lignocaine in the patients is a consequence of stimulation of hepatic first‐pass metabolism by antiepileptic drugs. 1979 Blackwell Science Ltd