| Indication |
For the treatment of the signs and symptoms of idiopathic
Parkinson's disease. Also used for the treatment of restless legs
syndrome. |
| Pharmacodynamics |
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. |
| Mechanism of action |
Ropinirole binds the dopamine receptors D3 and D2.
Although the precise mechanism of action of ropinirole as a treatment
for Parkinson's disease is unknown, it is believed to be related to its
ability to stimulate these receptors in the striatum. This conclusion is
supported by electrophysiologic studies in animals that have
demonstrated that ropinirole influences striatal neuronal firing rates
via activation of dopamine receptors in the striatum and the substantia
nigra, the site of neurons that send projections to the striatum. |
| Absorption |
Absolute bioavailability is 55%, indicating a first pass effect. Food does not affect the extent of absorption. |
| Volume of distribution |
|
| Protein binding |
40% bound to plasma proteins with a blood-to-plasma ratio of 1:1. |
| Metabolism |
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%). |
| Route of 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. |
| Half life |
6 hours |
| Clearance |
- 47 L/hr [after oral administration to Parkinson’s disease patients and patients with Restless Legs Syndrome]
|
| 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. |
