MicroRNAs as novel biomarkers for rivaroxaban therapeutic drug monitoring

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Eric Rytkin ◽  
Irina V. Bure ◽  
Pavel O. Bochkov ◽  
Kristina A. Akmalova ◽  
Karin B. Mirzaev ◽  
...  

Abstract Objectives The aim of this study is to assess micro-RNAs miR-142 and miR-39 as potential biomarkers for drug-monitoring of rivaroxaban among elderly patients with atrial fibrillation. Methods The study involved 57 patients with median (ME) age 87 years [80–94 years old] with nonvalvular atrial fibrillation admitted to a multidisciplinary hospital in Moscow. High-performance liquid chromatography with mass-spectrometry detection (HPLC-MS) was carried out to measure rivaroxaban concentrations. Carriership of CYP3A4 and ABCB1 was detected. MiRNA expression levels were measured. The activity of CYP3A4 isoenzyme was measured as the ratio of the concentrations of 6β-hydroxycortisol and cortisol. Results The miR-142 expression levels of patients with CC allelic variant polymorphism ABCB1 3435 C>T (rs1045642) were significantly higher compared to CT and TT variants 31.69 ± 1.60 vs. 34.06 ± 1.66 vs. 33.16 ± 1.77 (p=0.021). Carriers of TT allelic variant polymorphism ABCB1 rs4148738 had a higher concentration of the 6-beta-hydroxycortisol in urine compared to CC and CT variants 3,467.35 ± 1,055.53 vs. 3,453.52 ± 1,516.89 vs. 2,593.30 ± 1,172.52 (p=0.029). As for CYP3A4*22, the carriers of CC allelic variant had higher prothrombin time 14.10 ± 2.17 vs. 11.87 ± 0.60 and INR 1.31 ± 0.20 vs. 1.1 ± 0.06 but lower Quick’s value 74.52 ± 16.84 vs. 97.55 ± 10.54 (p=0.059). A positive correlation between the Ct miR-142 and the aPTT p=0.019 was noted. Also miR-142 has a correlation with Quick’s value p=0.095. There is no statistically significant connection between miR-142 and miR-39 expression levels and the plasma concentration of rivaroxaban (b coefficient=−2.055, SE 3.952, p=0.605 and b coefficient=1.546, SE 9.887, p=0.876 in the linear regression model respectively). Conclusions This study has assessed new potential biomarkers for rivaroxaban therapeutic drug monitoring: miR-142 and miR-39.

Author(s):  
Maria Mercedes De Zan

Chemometric optimization and validation of a method based on High Performance Liquid Chromatography (HPLC) using core – shell particles for the determination of Vancomycin (VMC) in human plasma is reported. The combination of the efficiency of the core-shell particles and the benefits of the design of experiments allowed the successful determination of VCM, even in presence of several interferents. Selectivity, linearity, accuracy and precision were accomplished according to the European Medicines Agency (EMA) guideline, within the concentration range of 1.00 – 60.0 μg/mL of VCM. It is noteworthy that this method requires small amount of sample and solvents, and the sample treatment is simple and no time-consuming. Thus, this method becomes a simple and high-throughput alternative to therapeutic drug monitoring in treated patients, as well as an analytical procedure that conforms to the principles of the green chemistry.


2019 ◽  
Vol 17 (5) ◽  
pp. 447-458
Author(s):  
Irene Aicua-Rapun ◽  
Pascal André ◽  
Jan Novy

Epilepsy is considered the most frequent severe neurological condition but most patients treated with medication become seizure free. The management of treatment, however, is highly empirical, mainly relying on observation. A closed-loop therapy for epilepsy would be very valuable for more efficient treatment regimens. Here we discuss monitoring treatment (therapeutic drug monitoring) and the potential developments in this field, as well as providing a review of potential biomarkers that could be used to monitor the disease activity. Finally, we consider the pharmacogenetic input in epilepsy treatment.


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