Kinetics of disopyramide in decreased hepatic function

Summary

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 · min⁻¹ (IHD group) until steady-state was achieved. A significant (p<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 µmol·l⁻¹ was 45.5% and 19.4% in the DHF and IHD groups, respectively. A negative correlation (r=−0,751,p<0.05, and r=−0.827,p<0.01 in the IHD and DHF patients, respectively) between the free fraction of disopyramide and alpha₁-acid glycoprotein was observed. The serum concentration of alpha₁-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.