1 The percentage of lignocaine free in the plasma of ten females receiving oral contraceptive medication was significantly greater than in 17 males of similar age (18-42 years). 2 In the same subjects the percentage of diazepam free in plasma was significantly greater in the contraceptive treated group than in 11 contraceptive-free females and significantly greater in contraceptive-free females than in males.3 The differences in lignocaine binding were almost completely attributable to changes in a,-acid glycoprotein concentration, which is reduced by oestrogens. The binding of diazepam was significantly related to albumin, a,-acid glycoprotein and non-esterified fatty acid concentrations which together were related to 55% of the variation in the binding of this basic compound.

The effects of myocardial infarction (MI) on lidocaine disposition were investigated in eight patients during a constant infusion of 2 mg/min. Plasma lidocaine binding and total plasma and free lidocaine concentrations were measured 12, 24, 36, and 48 hr after beginning therapy and were related to alpha 1-acid glycoprotein (AAG) concentrations. By 48 hr total plasma lidocaine and AAG concentrations had risen, as had plasma lidocaine binding. Because of enhanced binding, free lidocaine concentrations did not change significantly over this time. There was a correlation between AAG and the binding ratio for lidocaine (r = 0.87) and between AAG and total plasma lidocaine concentrations (r = 0.81). The data suggest that the rise in AAG seen after MI is responsible for enhanced plasma lidocaine binding and may, at least in part, be related to lidocaine cumulation.

1 The plasma concentration of alpha 1‐acid glycoprotein (AAG) was significantly greater in 27 epileptic subjects receiving anticonvulsants compared with 27 age‐ and sex‐matched drug‐free control subjects. 2 Increased AAG concentration was associated with enhanced lignocaine binding in the plasma of epileptics. 3 Increased AAG concentration was also associated with a redistribution of lignocaine out of red cells and into plasma thus lowering the blood to plasma concentration ratio. 4 Enhanced lignocaine binding in epileptics receiving anticonvulsant therapy may result in lower free (unbound) plasma concentrations of the drug compared to normal subjects with equivalent total plasma lignocaine concentrations.

1 Blood plasma and free lignocaine concentrations have been measured 12 h after beginning a constant infusion of 2 mg/min and again at the end of the infusion (36‐72 h) in five patients with myocardial infarction (MI) and compared with five control patients who did not develop objective evidence of MI. 2 In MI patients, total plasma concentration rose significantly between 12 h and the end of infusion. Because of an increase in alpha 1 acid glycoprotein (AAG) plasma binding increased, so that free drug concentration did not change. The rise in whole blood concentration was less than that in plasma as a result of drug redistribution out of red cells due to enhanced binding. 3 In control patients, neither blood nor plasma concentrations changed with time and plasma binding remained constant. Free drug concentrations, however, rose slightly. 4 The concentrations of GX and MEGX remained unchanged in all patients, but the ratio of lignocaine/MEGX concentrations fell in controls but rose in MI patients. 5 Pharmacokinetic modelling suggested that at least some of the rise in blood lignocaine concentration was due to reduced clearance resulting from enhanced plasma binding. 6 We conclude that the rise in AAG following MI is responsible for increased plasma binding and drug redistribution within blood. These changes, together with a reduction in lignocaine clearance, can explain much of the phenomenon of lignocaine accumulation in MI.

In 25 clinical samples serum lidocaine concentrations fell from a mean of 6.5 +/- 2.1 mg/L (mean +/- SD) to 4.9 +/- 1.8 mg/L (p less than 0.001) when the blood sample was allowed to make contact with the stopper of the Vacutainer collection tube. In vitro experiments showed that this effect of the stopper occurred only with whole blood and was dependent on sample concentration. The plasma binding of lidocaine decreased from a normal value of 56% +/- 2.2 (mean +/- SD) to 28% +/- 2.2 (p less than 0.001) when exposed to the Vacutainer stopper. We conclude that a chemical leached from such stoppers displaces lidocaine from its plasma-binding sites and that the drug is then redistributed into the erythrocytes, producing spuriously low lidocaine concentrations in plasma or serum. Such artifacts are important in therapeutic drug monitoring and can lead to erroneous clinical decisions.