Drug Groups

approved; investigational

Description

Ropinirole is a non-ergoline dopamine agonist, manufactured by GlaxoSmithKline. It is used in the treatment of Parkinson's disease, and is also one of two medications in the United States with an FDA-approved indication for the treatment of restless legs syndrome (the other being Pramipexole). [Wikipedia]

Indication

For the treatment of the signs and symptoms of idiopathic Parkinson's disease. Also used for the treatment of restless legs syndrome.

Pharmacology

Ropinirole is a nonergot dopamine agonist with high relative in vitro specificity and full intrinsic activity at the D₂ subfamily of dopamine receptors, binding with higher affinity to D₃ than to D₂ or D₄ receptor subtypes. The relevance of D₃ receptor binding in Parkinson's disease is unknown. The mechanism of ropinirole-induced postural hypotension is presumed to be due to a D₂ -mediated blunting of the noradrenergic response to standing and subsequent decrease in peripheral vascular resistance.

Toxicity

Symptoms of overdose include agitation, chest pain, confusion, drowsiness, facial muscle movements, grogginess, increased jerkiness of movement, symptoms of low blood pressure (dizziness, light-headedness)upon standing, nausea, and vomiting.

Affected Organisms

Biotransformation

Hepatic. Ropinirole is extensively metabolized to inactive metabolites via N -despropylation and hydroxylation pathways, largely by the P450 isoenzyme CYP1A2. N-despropyl ropinirole is the predominant metabolite found in urine (40%), followed by the carboxylic acid metabolite (10%), and the glucuronide of the hydroxy metabolite (10%).

Absorption

Absolute bioavailability is 55%, indicating a first pass effect. Food does not affect the extent of absorption.

Half Life

6 hours

Protein Binding

40% bound to plasma proteins with a blood-to-plasma ratio of 1:1.

Elimination

Ropinirole is extensively metabolized by the liver to inactive metabolites, and less than 10% of the administered dose is excreted as unchanged drug in urine.

Distribution

* 7.5 L/kg
* 525 L

Clearance

* 47 L/hr [after oral administration to Parkinson's disease patients and patients with Restless Legs Syndrome]

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