A comparative study of antipyrine and lignocaine disposition in normal subjects and in patients treated with enzyme-inducing drugs.
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.
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000494:pharmacology*; D000983:Antipyrine / Q000378:metabolism*; D001682:Biological Availability; D004790:Enzyme Induction / Q000187:drug effects; D005937:Glucaric Acid / Q000652:urine; D006801:Humans; D007700:Kinetics; D008012:Lidocaine / Q000378:metabolism*; D008875:Middle Aged
D000927:Anticonvulsants; D008012:Lidocaine; D005937:Glucaric Acid; D000983:Antipyrine