Prolonged variability in plasma protein binding of disopyramide after acute myocardial infarction.

Abstract

1 Disopyramide plasma binding was determined in vitro in plasma from 20 patients with acute myocardial infarction (aged 35-79 years) and in 20 age and sex matched healthy subjects. Plasma samples were collected on days 1, 5 and 12 after infarction and when the patient returned to the outpatient clinic. 2 In healthy subjects there was a significant negative correlation between disopyramide free fraction and plasma alpha 1-acid glycoprotein (AAG) concentration. A similar correlation was observed in the patients with myocardial infarction, however this correlation was dependent on time elapsed after infarction. Disopyramide free fraction did not correlate with albumin concentration in either group. 3 Mean plasma AAG concentrations were increased by 63% within 5 days after infarction and had returned to initial levels some months later (73.5 +/- 7.8 days). On each of the four sampling days, a two to four fold individual variability in plasma AAG concentrations was observed. 4 Maximum increases in disopyramide plasma binding were shown on days 5 and 12 after infarction. These increases were dependent on both drug and AAG concentrations. Increases in fraction bound were greater at the higher drug concentrations. Within the usual therapeutic plasma range for disopyramide (2 to 5 mg/l), the mean increases in fraction bound, compared to day 1 data, varied from 22 to 45% respectively. 5 Sequential alteration in AAG concentration after infarction indicates that disopyramide plasma binding may not reach a steady state until some months after infarction. Prediction of the time to achieve this steady state would be difficult due to inter- and intra-patient variability in binding.