Effect of Rofecoxib on the Pharmacokinetics of Digoxin in Healthy Volunteers
| Autor: | David L. Ebel, Pat J. Larson, Jules I. Schwartz, René Verbesselt, Arturo G. Porras, Simonne Lens, Robert Lins, Barry J. Gertz, Marina De Smet |
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| Rok vydání: | 2001 |
| Předmět: |
Adult
Male Digoxin Cardiotonic Agents Cmax Administration Oral Pharmacology Placebo Lactones Double-Blind Method Pharmacokinetics Oral administration polycyclic compounds medicine Humans Cyclooxygenase Inhibitors Drug Interactions Pharmacology (medical) Sulfones cardiovascular diseases Adverse effect Rofecoxib Cross-Over Studies Chemistry digestive oral and skin physiology Middle Aged Crossover study carbohydrates (lipids) Female medicine.drug |
| Zdroj: | The Journal of Clinical Pharmacology. 41:107-112 |
| ISSN: | 0091-2700 |
| DOI: | 10.1177/00912700122009755 |
| Popis: | The authors examined the effect of the cyclooxygenase-2 (COX-2) inhibitor, rofecoxib, at steady state on the pharmacokinetics of digoxin following a single dose in healthy subjects. Each healthy subject (N = 10) received rofecoxib (75 mg once daily) or placebo for 11 days in a double-blind, randomized, balanced, two-period crossover study. A single 0.5 mg oral dose of digoxin elixir was administered on the 7th day of each 11-day period. Each treatment period was separated by 14 to 21 days. Samples for plasma and urine immunoreactive digoxin concentrations were collected through 120 hours following the digoxin dose. No statistically significant differences between treatment groups were observed for any of the calculated digoxin pharmacokinetic parameters. For digoxin AUC(0-infinity), AUC(0-24), and Cmax, the geometric mean ratios (90% confidence interval) for (rofecoxib + digoxin/placebo + digoxin) were 1.04 (0.94, 1.14), 1.02 (0.94, 1.09), and 1.00 (0.91, 1.10), respectively. The digoxin median tmax was 0.5 hours for both treatments. The harmonic mean elimination half-life was 45.7 and 43.4 hours for rofecoxib + digoxin and placebo + digoxin treatments, respectively. Digoxin is eliminated renally. The mean (SD) cumulative urinary excretion of immunoreactive digoxin after concurrent treatment with rofecoxib or placebo was 228.2 (+/- 30.8) and 235.1 (+/- 39.1) micrograms/120 hours, respectively. Transient and minor adverse events occurred with similar frequency on placebo and rofecoxib treatments, and no treatment-related pattern was apparent. Rofecoxib did not influence the plasma pharmacokinetics or renal elimination of a single oral dose of digoxin. |
| Databáze: | OpenAIRE |
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