Adjepon-Yamoah, Kenneth K.

2017-10-27T12:01:08Z

2017-10-27T12:01:08Z

1974

A gas-liquid chromatographic (GLC) method has "been developed for the simultaneous assay of lignocaine and its two active metabolites, ethylglycylxylidide (EGX) and glycylxylidide (GX), using a nitrogen-sensitive flame ionisation detector and single column temperature programming. A GLC method has also been developed for the assay of 4-hydroxyxylidine} a major metabolite of lignocaine. Lignocaine metabolism was studied in healthy volunteers following oral and intramuscular administration. The metabolism of the drug was also studied in hospital patients (a) undergoing anaesthesia and a variety of gynaecological surgical procedures, (b) with chronic liver disease and (c) with acute myocardial infarction and/or cardiac failure. The plasma antipyrine half-life "was measured in some of these patients as an independent measure of hepatic drug metabolising activity. In healthy volunteers lignocaine is extensively and rapidly metabolised to EGX, GX and 4-hydroxyxylidine. 2,6 xylidine and 4-hydroxy lignocaine and other unidentified metabolites were also present in the urine after lignocaine administration. The absorption of lignocaine was delayed in laparoscopy patients. The elimination of the drug from plasma was slow in patients undergoing anaesthesia and other minor gynaecological procedures. The elimination of antipyrine was not markedly altered by anaesthesia and/or surgery. Lignocaine absorption, metabolism and elimination were abnormal in four patients with chronic liver disease and the plasma antipyrine half-life was abnormally prolonged in two. During a constant intravenous infusion of lignocaine in patients with acute myocardial infarction or cardiac failure no 'steady state' plasma concentrations of the drug were reached and the concentrations rose progressively. The concentrations of lignocaine were high and potentially toxic levels were reached in the presence of cardiac failure and cardiogenic shock. There was a slow cumulation of EGX and GX in plasma during prolonged lignocaine infusion. The metabolism of lignocaine was impaired especially in patients with cardiac failure or cardiogenic shock. Antipyrine metabolism was abnormal in the patients with acute cardiac failure.

http://hdl.handle.net/1842/25365

The University of Edinburgh

Annexe Thesis Digitisation Project 2017 Block 14

Lignocaine metabolism in man

Thesis or Dissertation

Doctoral

PhD Doctor of Philosophy