Pharmacokinetics of lidocaine in man

Abstract

Plasma levels of lidocaine were measured in 5 normal male volunteers following both intravenous and oral administration of the drug. Each subject received a constant-rate intravenous infusion lasting for 60 minutes and an exponential intravenous infusion which allowed administration of the drug at an ever-decreasing rate having a half-life of 50 minutes.In each case the total dose of lidocaine was 250 mg. The subjects also received a 250 mg. and a 500 mg. oral dose administered in tablet form. The plasma level data were subjected to pharmacokinetic analysis with the use of a two-compartment open model to describe the lidocaine disposition. These calculations suggest that approximately 5 to 7 hours of constant intravenous infusion would be required to approach steady-state plasma levels in human subfects. The plasma level data after oral administration indicate that approximately 35 per cent of the 250 and 500 mg. oral doses reached the systemic circulation. Subfective symptoms typical of lidocaine were noted in some cases after the 500 mg. oral doses. Since these symptoms were noted when the blood levels of lidocaine were lower than those following intravenous administration, it is suggested that they may, in part, be due to a metabolite formed during the first passage of the drug through the liver.

Reducing Pain Experienced During Potassium Chloride Infusion in the Emergency Department

“…To ensure that the lignocaine dose we used was effective in controlling pain and had minimal risk for adverse event, we decided to use 3 mL of 1% lignocaine for in our study. Furthermore, Lim et al (14) has shown that this dose of lignocaine was effective for pain control both immediately and throughout a 2-hour infusion period, attributable to the duration of action of lignocaine [t 1/2 , 80-108 minutes (20,21)]. With the increased in sample size, our study had shown that lignocaine was able to reduce to pain associated with potassium chloride infusion.…”

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

“…Although this assumption is substantiated by carefully conducted stuLdies both in animals (Keenaghan & Boyes, 1972;Boyes eIla., 1970) and in man (Boyes et al, 1971;Huet ct al., 1979), it may not necessarily hold true for all experimental conditions in which the test could possibly be used.…”

“…Under these conditions, and provided absorption is complete and metabolism is first-order, any change in hepatic drug metabolizing capacity will result in proportional but opposite changes in the oral bioavailability of the drug (Wilkinson & Shand, 1975;Alvan, Piafsky, Lind & von Bahr, 1979;Sotaniemi et al, 1978;Perucca & Richens, 1979a,b;Pantuck, Hsiao, Conney, Garland, Kappas, Anderson & Alvares, 1976) which, in turn, can be used as an indirect index of enzyme-induction or inhibition. Although the theoretical aspects of these principles have been considered in detail (Wilkinson & Shand, 1975;Perrier & Gibaldi, 1974;Rowland, 1972) (Stenson, Constantino & Harrison, 1971), primarily due to metabolic biotransformation by an enzymatic system which involves the mixed function oxidase (Strong, Parker & Atkinson, 1973;Hollunger, 1960;Keenaghan & Boyes, 1972) and has been shown to be inducible in animals (Di Fazio & Brown, 1972) and in man (Perucca & Richens, 1979b;Heinonen, Takki & Jahro, 1979); ii) virtually complete absorption from the gastrointestinal tract (Keenaghan & Boyes, (Bending, Bennett, Rowland & Steiner, 1976;Perucca, 1979;Boyes et al, 1971); iv) its previous use as a model drug in experiments designed to evaluate the perfusion-limited pharmacokinetic model in animals (Rane, Wilkinson & Shand, 1977;Branch, Shand, Wilkinson & Nies, 1973;Benowitz, Forsyth, Melmon & Rowland, 1974) and in man (Perucca & Richens, 1979b). This study provides further evidence in support of the hypothesis that the reduction of the oral bioavailability of lignocaine in epileptic patients is due to induction of the first-pass metabolism of the latter drug (Perucca & Richens, 1979b).…”

Reduction of oral bioavailability of lignocaine by induction of first pass metabolism in epileptic patients.

“…Lignocaine is almost ideal as a model drug because (i) it is subject to high hepatic clearance in man, as indicated by a high liver extraction ratio (Stenson, Constantino & Harrison, 1971) and evidence of extensive first-pass metabolism on oral administration (Boyes, Scott, Jebson, Godman & Julian, 1971;Bending, Bennett, Rowland & Steiner, 1976); (ii) it is metabolized by an enzymatic system in the liver which involves the mixed function oxidase (Hollunger, 1960; K^enaghan & Boyes, 1972; Bahr, Fellenius 8' Ft .d, 1972;Strong, Parker & Atkinson, 1973) and which is induced by phenobarbitone treatment the dog (Di Fazio & Brown, 1972); (iii) it has been previously selected to test the perfusion limited model in animal studies (Branch, Shand, Wilkinson & Nies, 1973;Benowitz, Forsyth, Melmon & Rowland, 1974a;Benowitz, Forsyth, Melmon & Rowland, 1974b;Rane, Wilkinson & Shand, 1977) and (iv) it is relatively safe at the plasma concentrations achieved in our subjects. This study adds further information to the question of lignocaine bioavailability on oral administration.…”