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 Dglucaric 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 bioavailability 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.

Effect of low‐dose phenobarbitone on five indirect indices of hepatic microsomal enzyme induction and plasma lipoproteins in normal subjects [letter]

“…Although the small number of subjects included in the present study does not allow a precise evaluation of the data in statistical terms, the reduction in oral availability of lignocaine, a putative measure of induction of first-pass metabolism (Perucca & Richens, 1979;Perucca et al, 1980) (Ohnhaus, Kirchof & Peheim, 1979). The observation that the serum yglutamyl-transpeptidase.…”

“…We have therefore decided to evaluate the enzyme-inducing properties of low doses of phenobarbitone (15 and 30 mg daily respectively) following repeated administration in normal volunteers. induction have been measured: antipyrine clearance (Stevenson, 1977), oral availability of lignocaine (Perucca et al, 1980), serum y-glutamyl-transpeptidase activity (Whitfield et al, 1973) and urinary excretion of 6-,8-hydroxycortisol (Ohnhaus & Park, 1979) and D-glucaric acid (Hunter et al, 1971). In view of the evidence that enzyme-induction may be responsible for biochemical disturbances in lipid metabolism (Perucca, 1978) (1980).…”

The effects of enzyme induction and enzyme inhibition on labetalol pharmacokinetics.

“…The bioavailability of cimetidine (Puurunen & Pelkonen, 1979), inlignocaine and of paracetamol is reduced in creases the bioavailability of propranolol (Feely patients taking anticonvulsant drugs known to et Heagerty et al, 1981) and chlorproduce enzyme induction (Perucca & Richens methiazole . Labetalol, a 1979a, b;Perucca et al, 1980). In contrast, an combined a-and ,-adrenoceptor antagonist, * Present address: Department of Medicine, Freedom is lipid soluble and undergoes high first pass Fields Hospital, Plymouth PL4 7LY extraction in man (Martin et al, 1976;Homeida 393 et al, 1978).…”

Antipyrine kinetics in liver disease and liver transplantation

“…7 It is an ideal drug for such studies because it is completely and rapidly absorbed from the gastrointestinal tract, is distributed in total body water with negligible binding to tissue or plasma proteins, is almost quantitatively metabolized in the liver, 7 and is a low-clearance drug with single-compartment kinetics. 9 Moreover, the clearance of antipyrine increases significantly in patients who receive enzyme-inducing agents such as phenytoin 10,11 and is reduced significantly in patients with liver disease as well as in patients receiving drugs that inhibit microsomal enzyme systems such as cimetidine. 12,13 The reported antipyrine arithmetic X ̅ (±SD) CL and t 1/2 values in normal subjects are 38.4 ± 4.4 ml/min and 10.3 ± 0.6 hours.…”