Indications
Tafamidis is approved for the treatment of cardiomyopathy associated with both wild-type and hereditary transthyretin-mediated amyloidosis in adults. This condition is characterized by the abnormal deposition of transthyretin amyloid fibrils in the heart, leading·harmacodynamics
The primary mechanism of action of tafamidis involves the stabilization of transthyretin tetramers. By preventing·heir dissociation, tafamidis effectively reduces the availability of monomers, thereby inhibiting·he process of amyloid fibril formation. Tafamidis is administered once daily, benefiting·herapeutic window.
Absorption
Upon administration, tafamidis achieves a maximum concentration (Cmax) of 1430.93 ng·he time to reach this maximum concentration (Tmax) is approximately 1.75 hours when fasted and extended to 4 hours when fed. The area under the curve (AUC), representing·he total drug exposure over time, is calculated to be 47,864.31 ng·h/mL.
Metabolism
Tafamidis exhibits minimal first-pass or oxidative metabolism, with 90% of the drug remaining·hang·hat tafamidis is predominantly metabolized via glucuronidation, with the resulting·he bile. This metabolic pathway underscores the drug's consistent pharmacokinetic profile.
Mechanism of Action
Tafamidis is designed to address the underlying challenges associated with transthyretin-related disorders. Genetic mutations or inherent protein misfolding can destabilize transthyretin tetramers, resulting in their dissociation and subsequent aggregation within tissues, which ultimately impairs normal tissue function. Tafamidis exerts its effect by binding to the transthyretin tetramers at the thyroxin binding sites. This binding action stabilizes the tetramer conformation, thereby diminishing the availability of monomers that could participate in amyloid formation.
