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 (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.


CONCLUSIONS
At the doses administered, there was no pharmacokinetic interaction and no evidence of a pharmacodynamic interaction between digoxin and levetiracetam.
Levy
R H
RH
Department of Pharmaceutics, University of Washington, H-272 Health Sciences Building, Box 357610, Seattle, WA 98195, USA. rhlevy@u.washington.edu
Ragueneau-Majlessi
I
I
Baltes
E
E
D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D018592:Cross-Over Studies; D004077:Digoxin / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006706:Homeostasis; D006801:Humans; D000077287:Levetiracetam; D008297:Male; D008875:Middle Aged; D010889:Piracetam / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D012016:Reference Values; D012449:Safety
D000927:Anticonvulsants; D000077287:Levetiracetam; D004077:Digoxin; D010889:Piracetam