MIRAPEX®
Mechanism of action
Pharmacological properties
Pharmacotherapeutic group: dopamine agonist
ATC code: N04BC05.1,2
MIRAPEX® is a non-ergot 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.2
The precise mechanism of action of MIRAPEX® as a treatment for Parkinson's disease (PD) is unknown, although it is believed to be related to its ability to stimulate dopamine receptors in the striatum. This conclusion is supported by electrophysiologic studies in animals that have demonstrated that MIRAPEX® 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. The relevance of D3 receptor binding in Parkinson’s disease is unknown.2
Absorption1,2
The absolute bioavailability of MIRAPEX® is greater than 90%,1,2 indicating that it is well absorbed and undergoes little presystemic metabolism.2 The maximum plasma concentrations occur between 1 and 3 hours.1 The rate of absorption is reduced by food intake but not the overall extent of absorption.1 The average time-to-peak concentration for MIRAPEX® prolonged- release (PR) tablets is 6 hours.2
Distribution2
MIRAPEX® is extensively distributed, having a volume of distribution of about 500 L (coefficient of variation = 20%). It is about 15% bound to plasma proteins. MIRAPEX® distributes into red blood cells as indicated by an erythrocyte-to-plasma ratio of approximately 2.2
Metabolism2
MIRAPEX® is metabolized only to a negligible extent (<10%).No specific active metabolite has been identified in human plasma or urine.2
Elimination1
Renal excretion of unchanged MIRAPEX® is the major route of elimination and accounts for about 80% of dose. Approximately 90% of a 14C-labelled dose is excreted through the kidneys while less than 2% is found in the feces. The total clearance of MIRAPEX® is approx. 500 ml/min and the renal clearance is approx. 400 ml/min. The elimination half-life (t ½) varies from 8 hours in the young to 12 hours in the elderly.1
Footnotes:
-
PD,Parkinson's disease; PR, prolonged- release.
References:
-
Mirapex® Tablets 0.25mg & 1.0mg. approved package insert. Approved in 08 Oct 2019.
-
MIRAPEX® Prolonged-Release Tablets 0.375 mg & 0.75 mg & 1.5 mg. approved package insert. Approved in 08 Oct 2019.
