A comparative study of antipyrine and lignocaine disposition in normal subjects and in patients treated with enzyme‐inducing drugs.

Abstract

1 The disposition kinetics of lignocaine and antipyrine were compared in eight normal subjects and in eleven patients receiving chronic therapy with antiepileptic drugs. The urinary excretion of D‐glucaric acid (D‐GA) was measured in 16 subjects. 2 In patients treated with antiepileptic drugs antipyrine clearance and D‐GA excretion were significantly increased, whereas lignocaine biovailability was significantly reduced. 3 When all the subjects included in the study were considered, a significant positive correlation could be found between the apparent oral clearance of lignocaine (Dose/area under the blood concentration curve) and both antipyrine clearance (r = 0.73) and D‐GA excretion (r = 0.74). 4 When normal subjects and epileptic patients were considered separately, a significant positive correlation could be confirmed between the apparent oral clearance of lignocaine and both antipyrine clearance (r = 0.71) and D‐GA excretion (r = 0.76) in normal subjects, and between antipyrine clearance and D‐GA excretion (r = 0.75) in epileptic patients. 5 These results suggest that the reduction of the oral availability of lignocaine in epileptic patients is secondary to induction of first‐pass metabolism of the latter drug. 1980 The British Pharmacological Society