Rosiglitazone does not affect the steady-state pharmacokinetics of digoxin

Rosiglitazone is a potent insulin-sensitizing oral hypoglycemic agent of th e thiazolidinedione class that works through activation of the peroxisome p roliferator-activated receptor-gamma (PPAR-gamma) nuclear receptor and impr oves glycemic control in patients with non-insulin-dependent diabetes melli tus. The potential for a drug-drug interaction with oral digoxin was invest igated. Subjects received both of the study regimens in a random sequence: digoxin 0.375 mg plus matching placebo for rosiglitazone orally each mornin g for 14 days or digoxin 0.375 mg plus 8 mg rosiglitazone orally each morni ng for 14 days. There was a 14-day rr ashout period between een sessions. B lood and urine rr ere collected over 24 hours beginning on the morning of d ay 14 for measurement of digoxin concentrations. An equivalence statistical approach was used, with rosiglitazone considered to have no effect on the pharmacokinetics of digoxin if the 90% confidence interval (CI) for the rat io of digoxin plus rosiglitazone relative to digoxin plus placebo was compl etely contained within the range (0.80, 1.25) for the primary end points, A UC((0.24)), and C-24. Digoxin AUC((0.24)) and C-24 values were similar for digoxin 0.375 mg plus matching placebo (18.5 ng .h/ml and 0.579 ng/mL, resp ectively) and digoxin 0.375 mg plus rosiglitazone (19.1 ng h/ml and 0.594 n g/mL, respectively). Point estimates were 1.05 (90% CI: 1.01, 1.10) for AUC ((0.24)) and 1.04 (90% CI: 0.98, 1.11) for C-24. Oral and renal clearance w ere also similar between regimens. Digoxin alone or in combination with ros iglitazone rr as safe and well tolerated. The most common adverse experienc e was headache. Coadministration of digoxin with rosiglitazone had no signi ficant effect on the safety or steady-state pharmacokinetics of digoxin. (C ) 2000 The American College of Clinical Pharmacology.