Tiagabine, a novel antiepileptic agent: lack of pharmacokinetic interaction with digoxin.
OBJECTIVE
To assess the possibility of any clinically relevant pharmacokinetic interactions between tiagabine, a novel antiepileptic drug, and digoxin.


METHODS
Potential pharmacokinetic interactions between tiagabine and digoxin were investigated in an open-label, two-period cross-over study in healthy male volunteers. Thirteen volunteers, aged between 18 and 43 years, were randomised to receive digoxin (0.5 mg twice a day for 1 day, then 0.25 mg once a day for 8 days) either alone or co-administered with tiagabine (4 mg three times daily for 9 days). Following a 7-day washout period, volunteers crossed over to the other dosing regimen. Peak serum concentration, time to maximum serum, concentration, area under the serum concentration-time curve from zero to 24 h and steady state serum concentration were calculated for digoxin and compared between treatment groups.


RESULTS
No statistically significant differences between treatment groups were observed for any of the derived digoxin pharmacokinetic parameters. The most common adverse events reported during digoxin alone and in combination with tiagabine were somnolence and headache; an overall greater frequency of adverse events was reported during combined treatment. Adverse events were generally mild in nature; no serious adverse events were reported.


CONCLUSIONS
At the doses administered, there is no evidence of a pharmacokinetic interaction between digoxin and tiagabine in healthy male volunteers.
Novo Nordisk A/S, Bagsvaerd, Denmark.
S
S
Snel
J A
JA
Jansen
P C
PC
Pedersen
J H
JH
Jonkman
P N
PN
van Heiningen
D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004077:Digoxin / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D004361:Drug Tolerance; D006801:Humans; D008297:Male; D009557:Nipecotic Acids / Q000009:adverse effects / Q000493:pharmacokinetics*; D000078308:Tiagabine
D000927:Anticonvulsants; D009557:Nipecotic Acids; D004077:Digoxin; D000078308:Tiagabine