Pharmacotherapeutic group: DOPAMINERGIC AGONISTS. ATC Code: N04BC08.
Pharmacology: Pharmacodynamics: Mechanism of action: Piribedil: dopaminergic agonist (stimulates dopamine receptors and the cerebral dopaminergic pathways).
In humans, the mechanism of action is demonstrated by the clinical pharmacology studies: stimulation of "dopaminergic" type cortical electrogenesis both while awake and during sleep; clinical activity on the different functions controlled by dopamine, with this activity being demonstrated via the use of behavioural or psychometric scales.
In addition, piribedil results in an increase in femoral blood flow (the existence of dopaminergic receptors in the femoral vascular bed explains the action of piribedil on peripheral circulation).
Pharmacokinetics: Absorption: Piribedil is absorbed rapidly.
Distribution: The maximum concentration is reached one hour after oral administration of piribedil. Plasma elimination is biphasic and is composed of a first phase characterised by a half-life of 1.7 hours and a second, slower phase characterised by a half-life of 6.9 hours.
Biotransformation: Metabolism of piribedil is intense, with two main metabolites: (a hydroxylated derivative and a dihydroxylated derivative).
Elimination: Piribedil is excreted essentially in the urine: 68% of the piribedil absorbed is excreted by the renal route in the form of metabolites and 25% is excreted in bile.
Pharmacokinetic/pharmacodynamics correlations: The tablet containing 50 mg of sustained-release piribedil allows in vivo gradual absorption and release of the active ingredient.
The kinetic studies conducted in humans show extension of the therapeutic coverage which exceeds 24 hours.
Urinary excretion is approximately 50% at the 24th hour and is total at the 48th hour.
Toxicology: Preclinical safety data: Subchronic or chronic administration of piribedil has been well-tolerated in animals. No teratogenic potential has been demonstrated for piribedil in animals. In vitro and in vivo tests have shown no genotoxic potential. No carcinogenicity studies have been conducted.