Disopyramide pharmacokinetics in the elderly after single oral administration

Disopyramide (D) kinetics were studied after single oral dose (200 mg) in ten elderly male patients (mean age: 75.5 yrs) without clinical or laboratory signs of hepatic, renal or cardiac disease, and in six healthy male subjects. They were all non smokers and had not taken alcohol for at least 10 days. Peak plasma concentration and area under the curve (AUCo-oo) were 54% and 51% respectively higher in the elderly group, whereas plasma half life was virtually the same in both groups (about 9 hrs).

The major D metabolite, mono-N-desisopropyldisopyramide (MND), showed a tendency towards an increase of AUCo-24h and T1/2 but did not reach the 5% significance level. Eight of the ten elderly patients but only tow of the six young subjects complained of anticholinergic side effects. On the basis of the pharmacokinetic changes observed (and provided that plasma protein binding is unchanged), D oral dose should be reduced by 1/3, without modifying the dosage interval.