On the role of alpha 1-acid glycoprotein in lignocaine accumulation following myocardial infarction.
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.
D000328:Adult; D000368:Aged; D001711:Biotransformation; D001798:Blood Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D008012:Lidocaine / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009203:Myocardial Infarction / Q000378:metabolism*; D009961:Orosomucoid / Q000378:metabolism*; D011485:Protein Binding; D013997:Time Factors
D001798:Blood Proteins; D009961:Orosomucoid; D008012:Lidocaine