Variation of tafamidis plasma levels during the treatment of TTR amyloidosis patients with Glu89Gln mutation.

Abstract

The transthyretin kinetic stabilizer tafamidis, used as a first-line therapy of amyloidosis patients, binds selectively to the transthyretin protein structure and thus prevents its dissociation. The limited information regarding tafamidis application in Glu89Gln amyloidosis patients imposed our research team to determine and evaluate its individual mean plasma levels and their biological variation. The present cohort study investigated Bulgarian amyloidosis patients, grouped by gender, age, and therapy duration. A total of sixty patients aged 40-75years and therapy duration up to 9years were included. A precise and accurate high-performance liquid chromatography method with ultraviolet detection was used for plasma concentration measurement. Mean plasma concentrations were 5.13 ± 2.64µmol/L and showed low intra-individual (18.50%) and high inter-individual variability (51.43%). No significant difference was observed between tafamidis plasma levels and therapy duration with p = 0.5941 (p < 0.05 considered significant), but a significant positive correlation was found between plasma concentration, gender, and age with obtained results about p-value 0.0001 and 0.0235, respectively. The summary results of the study showed differences that may be based on some specific clinical features of the Glu89Gln mutation.