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Dose optimisation of tacrolimus with therapeutic drug monitoring and CYP3A5 polymorphism in myasthenia gravis patients.
Chen D1, Hou S2, Zhao M1, Sun X1, Zhang H2, Yang L1.
Eur J Neurol. 2018 Apr 3. doi: 10.1111/ene.13652.
The concentration of tacrolimus is affected by many factors. TDM and detection of CYP3A5 polymorphism gene was essential for dosage optimization in MG patients.
- BACKGROUND AND PURPOSE:
Tacrolimus was beneficial for treatment of myasthenia gravis (MG). And it has a narrow therapeutic range, therefore, therapeutic drug monitoring (TDM) is essential for tacrolimus to optimize dosage and prevent adverse reactions. However, no studies have explored the influencing factors of tacrolimus blood concentration in MG patients. Thus, we aimed to analyze the influencing factors and discuss how to optimal tacrolimus dosage for MG treatment.
The data of clinical characteristics, therapeutic drugs and adverse reactions of patients with MG who received tacrolimus were collected from 2013 to 2015 in Beijing Hospital. Tacrolimus whole-blood concentrations were measured by chemiluminescent microparticle immunoassay (CMIA) and CYP3A5*3 gene polymorphism was detected by digital fluorescence molecule hybridization fluorescence. Regression analysis was applied to analyze the influencing factors of blood concentrations and adverse reactions.
It was shown that there was a certain correlation between concentration and dosage. Furthermore, co-administration of proton pump inhibitor (PPI) and clarithromycin and CYP3A5*3 gene polymorphism could significantly increase the tacrolimus whole blood levels. The adverse reaction was related
- to blood concentration, CYP3A5 genetic polymorphisms and combined medication though logistic regression analysis.