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

Objective: This study was undertaken to determine whether levetiracetam (Ke ppra (TM)) affected the pharmacokinetic or pharmacodynamic profile of digox in in healthy adults. Methods: Seven men and four women (19-48 years old) c ompleted this double-blind, placebo-con trolled study. Each received digoxi n 0.25 mg once daily (0.5 mg on day 1) during the 1-week run-in period, fol lowed by two 1-week periods of coadministration of digoxin with levetiracet am (2000 mg/day) or placebo in a two-way crossover design. The pharmacokine tics of digoxin and levetiracetam were assessed by analysis of blood sample s. ECG recordings were taken to monitor effects of levetiracetam on digoxin pharmacodynamics. Results: The ratios of geometric means, using a 90% conf idence 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 pharm acodynamic parameters did not differ significantly between levetiracetam an d placebo administration. Furthermore, the pharmacokinetics of levetiraceta m were not altered in the presence of digoxin. Co-administration of levetir acetam and digoxin was well tolerated. Conclusion: At the doses administere d, there was no pharmacokinetic interaction and no evidence of a pharmacody namic interaction between digoxin and levetiracetam. (C) 2001 Elsevier Scie nce B.V. All rights reserved.