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

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Abstract

Purpose

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.

Methods

The present cohort study investigated Bulgarian amyloidosis patients, grouped by gender, age, and therapy duration. A total of sixty patients aged 40–75 years and therapy duration up to 9 years were included. A precise and accurate high-performance liquid chromatography method with ultraviolet detection was used for plasma concentration measurement.

Results

Mean plasma concentrations were 5.13 ± 2.64 µmol/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.

Conclusion

The summary results of the study showed differences that may be based on some specific clinical features of the Glu89Gln mutation.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors are thankful to UMBAL Alexandrovska Hospital, Department of Neurology, for providing human plasma samples for conducting the experiments.

Funding

This work was kindly supported by Medical University-Sofia, Medical Science Council–Grant No. 121/24.06.2020.

Author information

Authors and Affiliations

  1. Department of Chemistry, Faculty of Pharmacy, Medical University, Sofia, 1000, Bulgaria

    M. Smerikarova, S. Bozhanov & V. Maslarska

  2. Clinic of Nervous Diseases, Alexandrovska University Hospital, Medical University, Sofia, Bulgaria

    I. Tournev

Authors
  1. M. Smerikarova
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  2. S. Bozhanov
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  3. I. Tournev
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  4. V. Maslarska
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Contributions

Vania Maslarska and Ivailo Tournev contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Miglena Smerikarova and Stanislav Bozhanov. The first draft of the manuscript was written by Miglena Smerikarova, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to M. Smerikarova.

Ethics declarations

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Research Ethics Committee at the Medical University of Sofia (RECMUS) with a certification no.1480/14.05.2020.

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Competing interests

The authors declare that they have no competing interests.

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Smerikarova, M., Bozhanov, S., Tournev, I. et al. Variation of tafamidis plasma levels during the treatment of TTR amyloidosis patients with Glu89Gln mutation. Eur J Clin Pharmacol 79, 1657–1664 (2023). https://doi.org/10.1007/s00228-023-03576-3

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  • DOI: https://doi.org/10.1007/s00228-023-03576-3

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