Lack of effect of eprosartan on the single dose pharmacokinetics of orally administered digoxin in healthy male volunteers.
OBJECTIVE
To study the effect of eprosartan, a nonbiphenyl tetrazole angiotensin II receptor antagonist, on digoxin pharmacokinetics in a randomized, open-label, two period, period balanced crossover study in 12 healthy men.


METHODS
Each subject received a single 0.6 mg oral dose of digoxin (Lanoxicaps 0.2 mg/capsule, Glaxo Wellcome) alone or following 4 days of dosing with eprosartan 200 mg orally every 12 h. Each study period was separated by a 14 day washout interval. Serial blood samples were obtained for up to 96 h after each digoxin dose for determination of digoxin pharmacokinetics. The effect of eprosartan on digoxin pharmacokinetics was assessed through an equivalence-type approach using AUC(0, t') as the primary endpoint.


RESULTS
For AUC(0, t'), the ratio of digoxin+eprosartan: digoxin alone was 0.99 with a 90% confidence interval (CI) of [0.90, 1.09]. For Cmax, the ratio was 1.00 with a 90% CI of [0.86, 1.17]. tmax was similar for both regimens. Both regimens were safe and well tolerated.


CONCLUSIONS
Based on AUC and Cmax data, it can be concluded that eprosartan has no effect on the pharmacokinetics of a single oral dose of digoxin.
Martin
D E
DE
SmithKline Beecham Clinical Pharmacology Unit, Presbyterian Medical Center of Philadelphia, University of Pennsylvania Health System 19104 USA.
Tompson
D
D
Boike
S C
SC
Tenero
D
D
Ilson
B
B
Citerone
D
D
Jorkasky
D K
DK
D000179:Acrylates / Q000008:administration & dosage / Q000494:pharmacology*; D000284:Administration, Oral; D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D019540:Area Under Curve; D018592:Cross-Over Studies; D004077:Digoxin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D008297:Male; D011863:Radioimmunoassay; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000378:metabolism; D013876:Thiophenes
D000179:Acrylates; D000889:Anti-Arrhythmia Agents; D000959:Antihypertensive Agents; D007093:Imidazoles; D007457:Iodine Radioisotopes; D011945:Receptors, Angiotensin; D013876:Thiophenes; C068373:eprosartan; D004077:Digoxin