Tacrolimus dose requirement based on the CYP3A5 genotype in renal transplant patients

Qu, Lihui; Lu, Yingying; Ying, Meike; Li, Bingjue; Weng, Chunhua; Xie, Zhoutao; Liang, Ludan; Lin, Ching‐Long; Yáng, Xiàn; Feng, Shi Ting; Wang, Yucheng; Shen, Xiaohua; Zhou, Qin; Chen, Ying; Chen, Zhimin; Wu, Jiang; Lin, Weiqiang; Shen, Yi; Qin, Jing; Xu, Hang; Xu, Feng; Wang, Junwen; Chen, Jianghua; Jiang, Hong; Huang, Hongfeng

doi:10.18632/oncotarget.18150

Cited by 7 publications

(3 citation statements)

References 18 publications

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“…CYP3A5 genetic polymorphisms are widely accepted to play an important role in tacrolimus metabolism. The relatively balanced distribution frequency of CYP3A5 in this study indicate that the CYP3A5*3 allele mutation is less common in Chinese than Caucasians, which facilitates to compare the effects of DDI between tacrolimus and nifedipine ( Chakkera et al, 2013 ; Qu et al, 2017 ).…”

Section: Discussionmentioning

confidence: 91%

CYP3A5 Genotype-Dependent Drug-Drug Interaction Between Tacrolimus and Nifedipine in Chinese Renal Transplant Patients

et al. 2021

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Purpose: The drug-drug interactions (DDIs) of tacrolimus greatly contributed to pharmacokinetic variability. Nifedipine, frequently prescribed for hypertension, is a competitive CYP3A5 inhibitor which can inhibit tacrolimus metabolism. The objective of this study was to investigate whether CYP3A5 genotype could influence tacrolimus-nifedipine DDI in Chinese renal transplant patients.Method: All renal transplant patients were divided into CYP3A5*3/*3 homozygotes (group I) and CYP3A5*1 allele carriers (CYP3A5*1/*1 + CYP3A5*1/*3) (group II). Each group was subdivided into patients taking tacrolimus co-administered with nifedipine (CONF) and that administrated with tacrolimus alone (Controls). Tacrolimus trough concentrations (C0) were measured using high performance liquid chromatography. A retrospective analysis compared tacrolimus dose (D)-corrected trough concentrations (C0) (C0/D) between CONF and Controls in group I and II, respectively. At the same time, a multivariate line regression analysis was made to evaluate the effect of variates on C0/D.Results: In this study, a significant DDI between tacrolimus and nifedipine with respect to the CYP3A5*3 polymorphism was confirmed. In group I (n = 43), the C0/D of CONF was significantly higher than in Controls [225.2 ± 66.3 vs. 155.1 ± 34.6 ng/ml/(mg/kg); p = 0.002]. However, this difference was not detected in group II (n = 27) (p = 0.216). The co-administrated nifedipine and CYP3A5*3/*3 homozygotes significantly increased tacrolimus concentrations in multivariate line regression analysis.Discussion: A CYP3A5 genotype-dependent DDI was found between tacrolimus and nifedipine. Therefore, personalized therapy accounting for CYP3A5 genotype detection as well as therapeutic drug monitoring are necessary for renal transplant patients when treating with tacrolimus and nifedipine.

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Section: Discussionmentioning

confidence: 91%

CYP3A5 Genotype-Dependent Drug-Drug Interaction Between Tacrolimus and Nifedipine in Chinese Renal Transplant Patients

et al. 2021

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“…This can be of relevance to better predict the dosage of antipsychotic drugs, allowing the rapid screening of patients and, thus, a personalized medicine approach, reducing the risk of toxic effects from medication [104]. The same method could help to define the right dose of tacrolimus that is an immunosuppressive drug often administered to patients who have undergone an organ transplant in order to reduce the risk of rejection [105], based on the CYP3A5 genotype in transplant patients [106,107]. The rapid and accurate CYP3A5 and MDR1 genetic polymorphisms analysis could also help to define the dosage of the immunosuppressive drug cyclosporine A, whose pharmacokinetic characteristics are extremely variable among individuals, to be administered during the early stage after renal transplantation [108,109].…”

Section: Me For Biomarker Detection In Personalized Therapy and Precimentioning

confidence: 99%

Microfluidics as a Novel Tool for Biological and Toxicological Assays in Drug Discovery Processes: Focus on Microchip Electrophoresis

et al. 2020

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The last decades of biological, toxicological, and pharmacological research have deeply changed the way researchers select the most appropriate ‘pre-clinical model’. The absence of relevant animal models for many human diseases, as well as the inaccurate prognosis coming from ‘conventional’ pre-clinical models, are among the major reasons of the failures observed in clinical trials. This evidence has pushed several research groups to move more often from a classic cellular or animal modeling approach to an alternative and broader vision that includes the involvement of microfluidic-based technologies. The use of microfluidic devices offers several benefits including fast analysis times, high sensitivity and reproducibility, the ability to quantitate multiple chemical species, and the simulation of cellular response mimicking the closest human in vivo milieu. Therefore, they represent a useful way to study drug–organ interactions and related safety and toxicity, and to model organ development and various pathologies ‘in a dish’. The present review will address the applicability of microfluidic-based technologies in different systems (2D and 3D). We will focus our attention on applications of microchip electrophoresis (ME) to biological and toxicological studies as well as in drug discovery and development processes. These include high-throughput single-cell gene expression profiling, simultaneous determination of antioxidants and reactive oxygen and nitrogen species, DNA analysis, and sensitive determination of neurotransmitters in biological fluids. We will discuss new data obtained by ME coupled to laser-induced fluorescence (ME-LIF) and electrochemical detection (ME-EC) regarding the production and degradation of nitric oxide, a fundamental signaling molecule regulating virtually every critical cellular function. Finally, the integration of microfluidics with recent innovative technologies—such as organoids, organ-on-chip, and 3D printing—for the design of new in vitro experimental devices will be presented with a specific attention to drug development applications. This ‘composite’ review highlights the potential impact of 2D and 3D microfluidic systems as a fast, inexpensive, and highly sensitive tool for high-throughput drug screening and preclinical toxicological studies.

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“…TGF-β1 production might correlate with reduced incidence of acute rejection, since it down-regulates Th1 responses and Th1 cytokine production [21]. Single-nucleotide polymorphisms are associated with the risk of some diseases and drug dose requirement in kidney recipients [23][24][25][26][27]. The current evidence indicates that TGF-β1 involves in the pathogenesis of acute rejection in patients with renal transplantation.…”

Section: Introductionmentioning

confidence: 99%

Relationship between TGF-β1 + 869 T/C and + 915 G/C gene polymorphism and risk of acute rejection in renal transplantation recipients

Zhou

Lin

et al. 2019

BMC Med Genet

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Background: This meta-analysis was conducted to assess the relationship between the transforming growth factorbeta 1 (TGF-β1) + 869 T/C gene polymorphism, + 915 G/C gene polymorphism, and the susceptibility of acute rejection in the recipients with renal transplantation. Methods: Relevant studies were searched and identified from the Cochrane Library and PubMed, and eligible investigations were recruited and data were calculated by meta-analysis. Results: In this study, we found no relationship between either TGF-β1 + 869 T/C or TGF-β1 + 915 G/C gene polymorphism and acute rejection susceptibility in patients with renal transplantation. No association between either gene polymorphism and acute rejection susceptibility in patients with renal transplantation in Caucasian, Asian, or African populations individually was found. Conclusion: The TGF-β1 + 869 T/C and + 915 G/C gene polymorphisms are not associated with acute rejection susceptibility in recipients with renal transplantation.

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Tacrolimus dose requirement based on the CYP3A5 genotype in renal transplant patients

Cited by 7 publications

References 18 publications

CYP3A5 Genotype-Dependent Drug-Drug Interaction Between Tacrolimus and Nifedipine in Chinese Renal Transplant Patients

CYP3A5 Genotype-Dependent Drug-Drug Interaction Between Tacrolimus and Nifedipine in Chinese Renal Transplant Patients

Microfluidics as a Novel Tool for Biological and Toxicological Assays in Drug Discovery Processes: Focus on Microchip Electrophoresis

Relationship between TGF-β1 + 869 T/C and + 915 G/C gene polymorphism and risk of acute rejection in renal transplantation recipients

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