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.
RCT Entities:
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.
Authors: Jules I Schwartz; Nancy G B Agrawal; Martin Wehling; Bret J Musser; Carol P Gumbs; Nicole Michiels; Marina De Smet; John A Wagner Journal: Br J Clin Pharmacol Date: 2008-09-24 Impact factor: 4.335