Pramipexole

Pharmacological properties

pramipexole, the active component of miraxol, is a dopamine agonist with high selectivity and specificity for dopamine receptors of the d2 subtype and has a predominant affinity for d3 receptors, it is characterized by complete internal activity.

Pramipexole alleviates Parkinsons motor disorders by stimulating the dopamine receptors of the striatum (striatum). Animal studies have shown that pramipexole inhibits dopamine synthesis and release. Pramipexole protects dopamine neurons from degeneration in response to ischemia or methamphetamine neurotoxicity.

The exact mechanism of action of pramipexole in the treatment of restless legs syndrome is unknown. Although the pathophysiology of restless legs syndrome is generally unknown, neuropharmacological data suggest involvement of the primary dopaminergic system.

Studies using positron emission tomography (PET) indicate the possibility of a minor dysfunction of the striatal presynaptic dopaminergic system affecting the pathogenesis of restless legs syndrome.

In vitro studies have shown that pramipexole protects neurons from the neurotoxic effects of levodopa. In studies involving volunteers, a dose-dependent decrease in prolactin levels was observed.

Pharmacokinetics Pramipexole is rapidly and completely absorbed after oral administration. Absolute bioavailability is 90%.

C_max in the blood plasma, they are noted for 1-3 hours. Against the background of food intake, the rate of absorption decreases, but not the general level of absorption.

Pramipexole is characterized by linear kinetics and, regardless of the dosage form, relatively minor fluctuations in plasma levels in different patients.

In humans, the binding of pramipexole to plasma proteins is very low (20%), and the distribution volume is large (400 L). In studies on rats, a high concentration of the drug in the brain tissue was noted (about 8 times higher compared to plasma).

Pramipexole is metabolized in humans only in small quantities.

Excretion of unchanged pramipexole by the kidneys is the most important way of elimination and is about 80%. About 90% of the dose labeled ¹⁴C is excreted by the kidneys, while less than 2% is determined in the feces. The total clearance of pramipexole is about 500 ml / min, and renal - about 400 ml / min. T_½ - from 8 hours in young patients and up to 12 hours in the elderly.

Indications

Treatment of symptoms of idiopathic Parkinson’s disease in adults, as monotherapy (without levodopa) or in combination with levodopa during the course of the disease to the later stages, when the effect of levodopa decreases or becomes unstable and a therapeutic effect fluctuates (“on-off” phenomenon).

Symptomatic treatment of idiopathic restless legs syndrome from moderate to severe in adults (doses not higher than 0.75 mg).

Application

All dosage information relates to pramipexole in the form of pramipexole dihydrochloride.

Tablets must be taken orally, washed down with water, regardless of food intake. The daily dose is divided equally into 3 doses.

Parkinsons disease. The start of treatment. As shown below, the dose should be increased gradually from the initial dose of 0.375 mg / day every 5-7 days. In cases where patients are not intolerant to the drug, the dose must be titrated until the maximum therapeutic effect is achieved.

If it is necessary to further increase the daily dose, it is increased by 0.75 mg weekly to a maximum of 4.5 mg / day.

It should be noted that drowsiness increases at doses of 1.5 mg / day.

Supportive treatment.An individual dose should be in the range of 0.375–4.5 mg / day. Usually, both at the beginning and in the late stage of the disease, the drug is effective, starting with a daily dose of 1.5 mg. In the future, the dose is corrected based on the clinical response and tolerance to the drug.

In clinical studies of pramipexole, some patients received doses of less than 1.5 mg. With progressive Parkinsons disease, a dose above 1.5 mg / day may be useful for patients for whom a dose reduction of levodopa with