No Effect of Rosuvastatin on the Pharmacokinetics of Digoxin in Healthy Volunteers

• Published in: Journal of clinical pharmacology 2002-12, Vol.42 (12), p.1352-1357
• Main Authors: Martin, Paul D., Kemp, John, Dane, Aaron L., Warwick, Mike J., Schneck, Dennis W.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Area Under Curve; Biological and medical sciences; Cardiotonic agents; Cardiovascular system; Cross-Over Studies; Digoxin - pharmacokinetics; Double-Blind Method; Drug Administration Schedule; Drug Interactions; Fluorobenzenes - blood; Fluorobenzenes - pharmacology; Fluorobenzenes - urine; General and cellular metabolism. Vitamins; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - blood; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Hydroxymethylglutaryl-CoA Reductase Inhibitors - urine; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Pyrimidines; Rosuvastatin Calcium; Sulfonamides; Time Factors
• ISSN: 0091-2700; 1552-4604
• DOI: 10.1177/0091270002042012008

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 AUC0‐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 (AUC0‐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.