Indications
Ubrogepant is specifically indicated for the acute treatment of migraines, with or without aura, in adult patients. The medication targets the underlying triggers of migraine headaches, providing relief from the debilitating symptoms associated with this condition.
Pharmacodynamics
Ubrogepant functions by inhibiting the activity of key neurotransmitters involved in the pathogenesis of migraines. This action helps alleviate the pain associated with migraine attacks. It is important to note that patients with severe hepatic or renal insufficiency may experience significantly increased exposure to ubrogepant. Consequently, dose adjustments are necessary for these individuals to prevent excessive exposure. Furthermore, ubrogepant is not recommended for patients with end-stage renal disease.
Absorption
Upon oral administration, ubrogepant reaches peak plasma concentrations (Tmax) within 0.7 to 1.5 hours. When taken with a high-fat meal, the Tmax is delayed by approximately 2 hours, and the maximum concentration (Cmax) is reduced by 22%, although the overall exposure (AUC) remains unchanged. Ubrogepant demonstrates dose-proportional pharmacokinetics across its recommended dosing range, ensuring predictable absorption at therapeutic levels.
Metabolism
Ubrogepant is predominantly metabolized in the body, with the CYP3A4 enzyme playing a major role in this process. The primary components found in human plasma are two circulating glucuronide conjugates and the unchanged parent drug. These glucuronide metabolites exhibit significantly reduced activity-6000-fold less-at the calcitonin gene-related peptide (CGRP) receptors, rendering them pharmacologically inactive.
Mechanism of Action
Ubrogepant functions as a potent antagonist of the calcitonin gene-related peptide (CGRP) receptor, effectively inhibiting the pathological processes involved in migraine attacks. According to the prevailing understanding of migraine pathophysiology, dysfunction within the central nervous system, particularly the trigeminal ganglion, is identified as a primary cause of the condition. Activation of this ganglion initiates the stimulation of trigeminal afferents projecting to the spinal cord, which then synapse on various intra- and extracranial structures responsible for sensing pain, such as the dura mater. This process leads to the transmission of pain signals via second-order ascending neurons to key brain regions, including the brainstem, hypothalamus, and thalamic nuclei, before reaching various cortical areas like the auditory, visual, and motor cortices. The trigeminal ganglion is known to enhance and sustain migraine headache pain through the activation of perivascular fibers and the release of pain-related molecules, most notably CGRP. During migraine episodes, levels of the α-isoform of CGRP, a known potent vasodilator expressed in primary sensory neurons, rise acutely and are considered crucial to migraine pathogenesis. CGRP not only facilitates vasodilation but also acts as a pronociceptive factor, modulating neuronal excitability to augment pain sensations. By competitively inhibiting CGRP at its receptors, ubrogepant interrupts this cycle, thereby curtailing migraine headache pain.
