Abstracts

RATIONALE: The study was undertaken to determine whether levetiracetam affected the pharmacokinetic or pharmacodynamic profile of digoxin, using a double-blind, placebo-controlled, two-way crossover design in healthy adults. METHODS: Seven male and four female subjects (18-48 years) completed the study. They were given digoxin 0.25 mg once a day (0.5 mg on the first day) for 1 week during a run-in period to achieve steady-state levels, followed by two 1-week periods of coadministration of digoxin with either levetiracetam (1000 mg bid) or placebo in a crossover design. The pharmacokinetics of both digoxin and levetiracetam were assessed by analysis of blood samples, and ECG recordings were taken to monitor the effects of levetiracetam on digoxin pharmacodynamics. RESULTS: The ratios of geometric means, using a 90% confidence interval, between coadministration of digoxin with levetiracetam or with placebo were 103.96% (99.18%, 108.95%) for AUCss, 100.87% (89.52%, 113.66%) for Cmax, 97.67% (82.76%, 115.26%) for PTF and 99.04% (90.98%, 109.00%) for Cmin, clearly demonstrating lack of interaction. In addition, levetiracetam pharmacokinetics after repeated digoxin administration did not differ from those previously reported in healthy volunteers. Mean levetiracetam maximal concentration was 35.8(6.6 ?g/mL at one-hour post dose and AUCss was 265(50 ?g.h/mL. Digoxin produced predictable changes in ECG, with increased PR-interval duration and decreased height of T-wave, but pharmacodynamic parameters did not differ significantly between levetiracetam and placebo. CONCLUSIONS: At the doses administered, there is no evidence of a pharmacokinetic or pharmacodynamic interaction between digoxin and levetiracetam.