Kinetics of disopyramide in decreased hepatic function

Abstract

The elimination kinetics of disopyramide was studied in 9 patients with decreased hepatic function (DHF) due to histologically verified cirrhosis of the liver, and in 11 patients with ischaemic heart disease (IHD). Disopyramide 100 and 150 mg was given intravenously as a bolus to the patients with IHD and DHF, respectively, followed by a continuous infusion of disopyramide 0.3 (DHF group) and 0.4 mg X min-1 (IHD group) until steady-state was achieved. A significant (p less than 0.001) positive correlation between the percentage unbound and total serum concentration of disopyramide was demonstrated in both groups. The percentage of unbound disopyramide at a total serum concentration of 5.9 mumol X l-1 was 45.5% and 19.4% in the DHF and IHD groups, respectively. A negative correlation (r = -0,751, p less than 0.05, and r = -0.827, p less than 0.01 in the IHD and DHF patients, respectively) between the free fraction of disopyramide and alpha 1-acid glycoprotein was observed. The serum concentration of alpha 1-acid glycoprotein, the major binding protein of disopyramide, was significantly lower in the patients with DHF. The clearance of unbound disopyramide and its total volume of distribution and half-life were significantly lower in the DHF patients. No difference in total elimination clearance could be demonstrated. The clinical implication of the present findings appear to be that the dosage of disopyramide should be reduced by 25% when it is given intravenously to patients with decreased hepatic function.

Quantitative and qualitative binding characteristics of disopyramide in serum from patients with decreased renal and hepatic function.

“…In patients with cirrhosis and abnormal biochemical variables serum concentration of AAG is reduced (Table 1) resulting in low binding of disopyramide. In a previous study (Bonde et al, 1986) we have demonstrated that the binding of disopyramide in such patients is significantly lower, even after correcting for differences in AAG concentrations, strongly suggestive of a qualitatively reduced binding of disopyramide in patients with cirrhosis and abnormal biochemical data. From the present study the reduced binding in group D patients can be explained by a reduced concentration of the alleged main binding fractions (Fr2 and Fr3).…”

Kinetics of disopyramide in decreased hepatic function

“…In a recent paper in this journal, Bonde et al (1986) described the kinetics of disopyramide in patients with decreased hepatic function ("DHF patients"). We were surprised by some statements in the discussion, which we think are not entirely correct, and which could mislead the reader.…”