No effect of rosuvastatin on the pharmacokinetics of digoxin in healthy volunteers.
The effect of rosuvastatin on the pharmacokinetics of digoxin was assessed in 18 healthy male volunteers in this double-blind, randomized, two-way crossover trial. Volunteers were dosed with rosuvastatin (40 mg once daily) or placebo to steady state before being given a single dose of digoxin 0.5 mg. Blood and urine samples for the measurement of serum and urine digoxin concentrations were collected up to 96 hours following dosing. The effect of rosuvastatin was assessed by constructing 90% confidence intervals (CIs) around the treatment ratios (rosuvastatin + digoxin/placebo + digoxin) for digoxin exposure. The geometric least square mean AUC(0-t) and Cmax of digoxin were only 4% higher when the drug was coadministered with rosuvastatin compared to placebo. The 90% CIs for both treatment ratios (AUC(0-t) = 0.88-1.24; Cmax = 0.89-1.22) fell within the prespecified margin of 0.74 to 1.35; therefore, no significant pharmacokinetic interaction occurred between rosuvastatin and digoxin. The geometric mean amount of digoxin excreted into the urine and its renal clearance were similar with rosuvastatin and placebo. These results demonstrate that rosuvastatin has no effect on the pharmacokinetics of digoxin. Coadministration of rosuvastatin and digoxin was well tolerated.
Martin
Paul D
PD
AstraZeneca, Alderley Park, Cheshire, United Kingdom.
Kemp
John
J
Dane
Aaron L
AL
Warwick
Mike J
MJ
Schneck
Dennis W
DW
D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D004077:Digoxin / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005464:Fluorobenzenes / Q000097:blood / Q000494:pharmacology* / Q000652:urine; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000097:blood / Q000494:pharmacology* / Q000652:urine; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides; D013997:Time Factors
D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D004077:Digoxin; D000068718:Rosuvastatin Calcium