Repeated administration of the novel antiepileptic agent levetiracetam does not alter digoxin pharmacokinetics and pharmacodynamics in healthy volunteers

Abstract

Objective: This study was undertaken to determine whether levetiracetam (Keppra™) affected the pharmacokinetic or pharmacodynamic profile of digoxin in healthy adults. Methods: Seven men and four women (19–48 years old) completed this double-blind, placebo-controlled study. Each received digoxin 0.25 mg once daily (0.5 mg on day 1) during the 1-week run-in period, followed by two 1-week periods of coadministration of digoxin with levetiracetam (2000 mg/day) or placebo in a two-way crossover design. The pharmacokinetics of digoxin and levetiracetam were assessed by analysis of blood samples. ECG recordings were taken to monitor effects of levetiracetam on digoxin pharmacodynamics. Results: The ratios of geometric means, using a 90% confidence interval, between coadministration of digoxin with levetiracetam or placebo were 103.96% (99.18%, 108.95%) for AUC ss, 100.87% (89.52%, 113.66%) for C max, 97.67% (82.76%, 115.26%) for PTF, and 99.04% (90.98%, 109.00%) for C min. Although digoxin produced predictable changes in ECG, its pharmacodynamic parameters did not differ significantly between levetiracetam and placebo administration. Furthermore, the pharmacokinetics of levetiracetam were not altered in the presence of digoxin. Co-administration of levetiracetam and digoxin was well tolerated. Conclusion: At the doses administered, there was no pharmacokinetic interaction and no evidence of a pharmacodynamic interaction between digoxin and levetiracetam.