Epistemis

Ropinirole

  • Non-Ergotic Dopamine Agonist / D2 Modulator

High affinity postsynaptic dopaminergic agonist agent with oxidative metabolism by hepatic cytochrome, indicated in Parkinson's and restless legs syndrome.

Mechanism

Chemical and Commercial Profile

Common trade names: Requip, Ropinirol Normon, Ropinirol Kern Pharma.
Group: Antiparkinsonian, non-ergot synthetic dopamine agonist.

Mechanism of Action

Ropinirole acts by selectively and specifically stimulating the striatal postsynaptic dopamine receptors D2 and D3, without affinity for the D1 receptors. By directly restoring dopaminergic transmission in the indirect and direct pathways, it depresses the state of muscle excitability characteristic of bradykinesia and parkinsonian rigidity.

Pharmacokinetics

Pharmacokinetics

  • Absorption: Rapid after oral intake; bioavailability of 50% due to moderate hepatic first-pass metabolism. The plasma peak is reached 1-2 hours after taking it on an empty stomach.
  • Distribution: Moderate binding to plasma proteins (40%). Large distribution volume of 7.5 L/kg. It easily crosses the blood-brain barrier.
  • Metabolism: Hepatic oxidative catalyzed mainly by the isoenzyme CYP1A2. Generates multiple inactive metabolites.
  • Excretion: Renal (90%) in the form of inactive conjugated metabolites and 10% in unaltered form.
  • Half-life (t1/2): 6 hours, requiring daily dosing in three doses or in a single dose using prolonged release formulations.

Indicators and dose

Indications

  • Treatment of Idiopathic Parkinson's Disease (in initial monotherapy to delay the need for levodopa, or in adjuvant combination to reduce motor fluctuations).
  • Symptomatic treatment of moderate to severe Restless Legs Syndrome (RLS).

Dosage and Settings

  • Initial monotherapy (immediate-release tablets): Start with 0.25 mg three times a day (0.75 mg/day total).
  • Titration: Increase progressively each week to a common clinical range of 3-9 mg/day (maximum of 24 mg/day).
  • Prolonged Release (Requip Retard): Allows a single daily intake at night, facilitating digestive tolerance.
  • Renal Failure: Does not require adjustments in ClCr 30 ml/min. In moderate renal failure, limit the dose to a maximum of 12 mg/day. Contraindicated in hemodialysis.
  • Liver Failure: Absolutely contraindicated in Child-Pugh B or C due to the hepatic CYP1A2-dependent elimination route.

Security

Contraindications

  • Renal failure in the terminal stage of dialysis (ClCr < 15 ml/min).
  • Severe decompensated liver failure (Child-Pugh C).

Adverse Effects (ADR)

  • CNS: Sudden sleep attacks, visual hallucinations (especially in the elderly), persecutory delusions, impulse control disorder (compulsive gambling, hypersexuality), postural dizziness, insomnia, dizziness.
  • Gastrointestinal: Temporary nausea, moderate stomach pain of early onset, gastroesophageal reflux of secondary muscular origin.
  • General: Persistent orthostatic hypotension, symmetrical peripheral edema in the lower extremities (moderate).

Clinical Interactions

  • CYP1A2 inhibitors: Fluvoxamine, ciprofloxacin, and estrogens double the serum concentration of ropinirole, requiring a preventive dose reduction.
  • CYP1A2 inducers: Tobacco is a potent inducer of the CYP1A2 pathway. Cessation or initiation of smoking may significantly alter ropinirole levels, requiring re-evaluation.

Pregnancy and Breastfeeding

FDA Category: C. Very limited human data; associates decreased embryonic growth in animals. Breastfeeding: Absolutely contraindicated. Like other dopaminergic drugs, it potently inhibits pituitary prolactin release reflexively, suppressing lactation, in addition to being excreted in breast milk.

Epistemis is educational review material. It is not a medical device, does not diagnose or prescribe treatment, and does not replace formal medical training, current clinical guidelines, or professional clinical judgment.

PreviousPramipexole
System
Antiepileptics and Antiparkinsonians
Cluster
Non-Ergotic Dopamine Agonist / D2 Modulator
Download Epistemis