Abstract
In order to elucidate the pharmacokinetic characteristics of digoxin in patients with Duchenne muscular dystrophy (DMD), digoxin was administered to nine patients with DMD and five healthy male volunteers.
The two-compartment model was fitted to the digoxin plasma concentration-timecurve, using the nonlinear least-squares regression program APAS following a singleoral administration of digoxin 7μg/kg.
The results were expressed as M± SE. The obtained pharmacokinetic parameterswere compared between DMD patients (n=9) and healthy volunteers (n=5).
The volume of distribution (Vdss) was significantly lower in DMD patients (5.87±0.43l·kg-1) than in normal volunteers (8.28±0.84l·kg-1) (P<0.05). The half-life in βphase (t1/2 β) was significantly shorter in DMD patients (16.93±2.17 hr) than innormal volunteers (33.73±5.20 hr) (P<0.05). The area under the curve (AUC0→∞) was significantly smaller in DMD patients (16.41±1.68ng·ml-1·hr) than in normalvolunteers (25.09±3.26ng·ml-1·hr) (P<0.05). The elimination rate constant (Kel) was significantly larger in DMD patients (0.29±0.04hr-1) than in normal volunteers (0.15±0.02hr-1) (P<0.05).
It is concluded that the dose of digoxin must be modified on the basis of these resultsin DMD patients.
