The effect of steady-state ropinirole on plasma concentrations of digoxin in patients with Parkinson's disease.
OBJECTIVE
The aim of this single-blind study was to assess the effect of ropinirole, a novel treatment for Parkinson's disease, on the steady-state pharmacokinetics and safety of digoxin in 10 patients with Parkinson's disease.


METHODS
There were three parts to the study: digoxin once daily plus placebo three times daily for 1 week; digoxin once daily plus ropinirole three times daily for 6 weeks; and digoxin once daily plus placebo three times daily for 1 week. Serial blood samples were collected over 24 h at the end of each part of the study for pharmacokinetic assessment. Pre-dose blood samples were collected on specific days throughout the study to assess the attainment of steady-state plasma levels of digoxin. The primary endpoints were AUC(0, tau) and Cmax for digoxin.


RESULTS
There was a mean decrease of 10% in digoxin AUC (0, tau) (90% CI: 0.79, 1.01) and a 25% decrease in digoxin Cmax (90% CI: 0.58, 0.97) when ropinirole was co-administered, compared with digoxin alone Cmin plasma values for digoxin, however, were fairly constant throughout the study (point estimates 0.99, 95% CI: 0.85, 1.15). Changes in trough levels of digoxin are believed to be the most reliable way of assessing steady-state concentrations of digoxin, and therefore the clinical significance of an interaction. Changes in Cmax are too readily influenced by other factors.


CONCLUSIONS
These results therefore indicate that on pharmacokinetic grounds no dose adjustment is necessary for digoxin co-administered with ropinirole.
Taylor
A
A
Drug Metabolism and Pharmacokinetics, SmithKline Beecham Pharmaceuticals, Welwyn, Herts, UK.
Beerahee
A
A
Citerone
D
D
Davy
M
M
Fitzpatrick
K
K
Lopez-Gil
A
A
Stocchi
F
F
D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000097:blood*; D000978:Antiparkinson Agents / Q000494:pharmacology*; D004077:Digoxin / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D010300:Parkinson Disease / Q000097:blood*; D010919:Placebos; D016037:Single-Blind Method
D000889:Anti-Arrhythmia Agents; D000978:Antiparkinson Agents; D007211:Indoles; D010919:Placebos; C046649:ropinirole; D004077:Digoxin