Creatine kinase elevation in chronic hepatitis B patients with telbivudine therapy: influence of telbivudine plasma concentration and single nucleotide polymorphisms of TK2, RRM2B, and NME4.

Autor: He T; Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, 200040, China., Chen B; Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, 200040, China., Li Y; Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, 200040, China., Song Y; Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, 200040, China., Wu J; Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, 200040, China., Xiong B; Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, 200040, China., Wang B; Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, 200040, China. Wangbin@huashan.org.cn., Long J; Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, 200040, China. 15111030044@fudan.edu.cn.
Jazyk: angličtina
Zdroj: European journal of clinical pharmacology [Eur J Clin Pharmacol] 2024 Jul; Vol. 80 (7), pp. 1029-1038. Date of Electronic Publication: 2024 Mar 19.
DOI: 10.1007/s00228-024-03674-w
Abstrakt: Purpose: To study the correlations of genetic variants of telbivudine phosphorylase kinases and telbivudine plasma concentration with creatine kinase elevation in chronic hepatitis B patients who received telbivudine.
Methods: An observational study was performed in China chronic hepatitis B patients receiving telbivudine therapy at 600 mg once daily. Plasma concentration was measured 12 h after taking telbivudine using ultra-performance liquid chromatography-tandem mass spectrometry and SNPs located in RRM2B, TK2, and NME4 was detected by MALDI-TOF mass spectrometry. All statistical analyses were performed with R 4.3.1 and all graphs were drawn by Origin 2023b and P value < 0.05 was considered statistically significant.
Results: A total of 140 patients receiving telbivudine therapy were recruited with a median plasma concentration of 952.49 (781.07-1238.98) ng/mL. The value of plasma concentration was proportional to the grade of creatine kinase elevation and the best telbivudine plasma concentration threshold to discriminate the grade 3/4 CK elevation was 1336.61 ng/mL. Multivariate analysis revealed that plasma concentration and rs3826160 were the independent risk factor of telbivudine-induced creatine kinase elevation. Patients with TC and CC genotype in rs3826160 not only had a higher incidence of creatine kinase elevation but also a higher plasma concentration than TT genotype carriers.
Conclusion: Chronic hepatitis B patients with TC and CC genotype in rs3826160 have high telbivudine plasma concentration are at risk of elevated creatine kinase.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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