Clinical Pharmacokinetics of Ropinirole

Ropinirole is a selective non-ergoline dopamine D₂ receptor agonist indicated for use in treating Parkinson’s disease. When taken as oral tablets, ropinirole is rapidly and almost completely absorbed, and it is extensively distributed from the vascular compartment. The bioavailability is approximately 50%. Ropinirole shows low plasma protein binding. The drug is inactivated by metabolism in the liver, and none of the major circulating metabolites have pharmacological activity. The principal metabolic enzyme is the cytochrome P450 (CYP) isoenzyme CYP1A2.

Ropinirole shows approximately linear pharmacokinetics when given as single or repeated doses, and is eliminated with a half-life of approximately 6 hours. Population pharmacokinetics have demonstrated that gender, mild or moderate renal impairment, Parkinson’s disease stage and concomitant illnesses or the use of several common concomitant medications have no effect on the pharmacokinetics of ropinirole. Clearance is slower for patients older than 65 years compared with those who are younger, and in women taking hormone replacement therapy compared with those who are not. The CYP1A2 inhibitor ciprofloxacin produced increases in the plasma concentrations of ropinirole when these 2 drugs were coadministered, but no interaction was seen with theophylline which, like ropinirole, is also a substrate for CYP1A2. There is no obvious plasma concentration-effect relationship for ropinirole.