Ropinirole

BRAND NAMES

Requip: It is available in the form of immediate release tablets and extended-release tablets with active ingredient ropinirole.

MECHANISM OF ACTION

Ropinirole is a dopamine agonist that does not require ergoline. Ropinirole has the highest affinity for D3 receptors, which are concentrated in the limbic parts of the brain and may account for some of the neuropsychiatric symptoms. Ropinirole's specific mechanism of action as a Parkinson's disease medication is uncertain, although it is thought to be connected to its capacity to selectively stimulate dopamine D2 receptors inside the caudate-putamen pathway in the brain. This system influences bodily mobility. Ropinirole has a low affinity for peripheral α2 adrenoreceptors and the 5HT-1 receptor. Ropinirole has no affinity for the D1-like receptors, benzodiazepines, or GABA receptors.

PHARMACOKINETICS

Absorption

Ropinirole is readily absorbed orally and achieves peak plasma concentrations 1 to 2 hours after administration. Approximately 50% of the medication is metabolized on the first pass, with absolute bioavailability ranging from 45% to 55%. The medicine reaches steady-state concentrations within two days of starting ropinirole. A high-fat diet may delay absorption, extend the Tmax by 2.5 hours, and reduce the Cmax by 25%; ropinirole is best absorbed while fasting.

Distribution

Ropinirole's plasma protein binding accounts for 40% of its volume of distribution, which is 7.5 L/kg.

Metabolism

The majority of ropinirole is broken down into inactive metabolites in the liver by N-despropylation and hydroxylation. The main enzyme involved in ropinirole metabolism is cytochrome P450 1A2.

Elimination

The ropinirole immediate-release tablet has an elimination half-life of approximately 6 hours, with less than 10% of the orally taken medication eliminated unaltered in urine.

PHARMACODYNAMICS

This medicine relieves or improves Parkinson's or restless leg syndrome symptoms by stimulating dopamine receptors, which regulate movement.

DOSAGE AND ADMINISTRATION

There are two oral formulations available: prolonged/extended-release tablets (2 mg, 4 mg, 6 mg, 8 mg, and 12 mg) and immediate-release tablets (0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg, and 5 mg). Three times a day is the recommended dosage for the immediate-release form and once a day for the extended-release type.

This drug has a therapeutic range of 0.4 to 6 ng/mL; however, due to their slower medication clearance, older patients (over 65) and women undergoing hormone replacement therapy (HRT) should use this drug with caution. A dose of 6 to 24 mg of the extended-release formulation is typically well tolerated in the treatment of Parkinson's disease (PD), and the physician can customize the dosage for each patient.

CONTRAINDICATIONS

Patients with a history of hypersensitivity or allergy reactions (urticaria, angioedema, rash, pruritus) to ropinirole or any of the excipients should not take ropinirole tablets.

DRUG INTERACTIONS

The CYP1A2 enzyme can lower the plasma levels of ropinirole and is activated by omeprazole and smoking. Fluvoxamine, mexiletine, and fluoroquinolones (such as ciprofloxacin and norfloxacin) all suppress CYP1A2. The administration of these medications may raise the medication's plasma level.

The clearance of ropinirole is decreased by hormone replacement treatment (HRT, high dose estrogens); dose adjustments may be necessary when initiating or discontinuing HRT.

The effectiveness of ropinirole can be decreased by the dopamine antagonists metoclopramide, phenothiazines, thioxanthenes, and butyrophenones. It is best to refrain from taking metoclopramide and ropinirole at the same time.

SIDE EFFECTS

The common side effects of Ropinirole include

• Abdominal pain
• Viral infection
• Vomiting
• nausea
• syncope
• asthenic condition
• drowsiness
• hallucination
• leg edema

Severe side effects include

• Dopamine agonist withdrawal syndrome
• Reversible dyskinesias
• Dermal eruptions
• Impulse control disorders
• Anterocollis pisa syndrome
• Peripheral edema

TOXICITY

Ropinirole can cause death when combined with alcohol, thus people who drink heavily should avoid using the medicine. A fatal dosage of up to six times the therapeutic dose is associated with death. Patients with liver insufficiency require thorough monitoring; a case report of liver damage is available. The medicine is predominantly metabolized in the liver, and the toxicity could be due to an immunological response or a toxic metabolite. Nausea, dizziness, hyperhidrosis, visual hallucinations, claustrophobia, palpitations, chorea, asthenia, and nightmares were the most commonly reported adverse events in individuals who took doses greater than 24 mg per day. Other symptoms observed in overdose patients included vomiting, agitation, chest discomfort, increased coughing, weariness, orthostatic hypotension, syncope, dyskinesia, somnolence, and confusion. According to a recent study, shock, and arrhythmias are the most likely causes of fatality associated with ropinirole overdose.