Benefits of minimizing immunosuppressive dosage according to cytochrome P450 3A5 genotype in liver transplant patients: findings from a single-center study

Wang, L.; Li, N.; Wang, M.X.; Lu, Shichun

doi:10.4238/2015.april.10.31

Cited by 7 publications

(5 citation statements)

References 16 publications

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“…From these, three ADEs (nephrotoxicity, hepatotoxicity, and hyperglycemia) were validated and found to be associated with the CYP3A5 polymorphism, rs776746 (PharmGKB level 2A or level 3 evidence). [32][33][34][35] Thus, we were able to validate our tacrolimus ADE-related genetic hypotheses, underscoring the accuracy of our text mining algorithm. More importantly, the generation of 119 new PG hypotheses highlights the significance of our translational research method in enabling the discovery of potentially new genetic mechanisms that may otherwise not have been explored through conventional DDI and PG research methods.…”

Section: Discussionmentioning

confidence: 58%

“…A total of 25 ADE terms were common between the DDI and DGI abstracts. From these, three ADEs (nephrotoxicity, hepatotoxicity, and hyperglycemia) were validated and found to be associated with the CYP3A5 polymorphism, rs776746 (PharmGKB level 2A or level 3 evidence) . Thus, we were able to validate our tacrolimus ADE‐related genetic hypotheses, underscoring the accuracy of our text mining algorithm.…”

Section: Discussionmentioning

confidence: 60%

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Translational Knowledge Discovery Between Drug Interactions and Pharmacogenetics

Wu¹,

Shendre

Zhang

et al. 2020

Clin Pharma and Therapeutics

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Clinical translation of drug‐drug interaction (DDI) studies is limited, and knowledge gaps across different types of DDI evidence make it difficult to consolidate and link them to clinical consequences. Consequently, we developed information retrieval (IR) models to retrieve DDI and drug‐gene interaction (DGI) evidence from 25 million PubMed abstracts and distinguish DDI evidence into in vitro pharmacokinetic (PK), clinical PK, and clinical pharmacodynamic (PD) studies for US Food and Drug Administration (FDA) approved and withdrawn drugs. Additionally, information extraction models were developed to extract DDI‐pairs and DGI‐pairs from the IR‐retrieved abstracts. An overlapping analysis identified 986 unique DDI‐pairs between all 3 types of evidence. Another 2,157 and 13,012 DDI‐pairs and 3,173 DGI‐pairs were identified from known clinical PK/PD DDI, clinical PD DDI, and DGI evidence, respectively. By integrating DDI and DGI evidence, we discovered 119 and 18 new pharmacogenetic hypotheses associated with CYP3A and CYP2D6, respectively. Some of these DGI evidence can also aid us in understanding DDI mechanisms.

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 60%

Translational Knowledge Discovery Between Drug Interactions and Pharmacogenetics

Wu¹,

Shendre

Zhang

et al. 2020

Clin Pharma and Therapeutics

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“…Data for tacrolimus dose and blood concentration were not reported in a number of studies (Table ). Some studies determined CYP3A5 genotype in both recipients and donors of liver grafts, while some of them determined or reported it for only recipients or donors of liver graft …”

Section: Resultsmentioning

confidence: 99%

“…Evaluation of parameters related to selection showed that in all of the studies, sample population was representative of the community and both genotype groups were selected from the same population except one in which patients with developed acute cellular rejection were selected, eleven studies did not obtain blood samples at the same time for all participants and that was one of the reasons for their exclusion from the analyses, seven studies did not begin their experiments from first post‐transplant day, when tacrolimus was administered for the first time . Two parameters were checked as confounders, and apart from five studies, others did not assess one or both of them. Appraisal of outcomes revealed that in 23 studies, outcomes of interest were not presented (eg, because of nonsignificant data) or presented improperly (eg, as median) which led to the exclusion of the study from the analyses or obligated us to estimate required data .…”

Section: Resultsmentioning

confidence: 99%

Effect of CYP3A5*1 expression on tacrolimus required dose after liver transplantation: A systematic review and meta‐analysis

Hendijani

Azarpira

Kaviani

2018

Clinical Transplantation

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We systematically collected eligible data to measure the effect of CYP3A5*1 expression on personalized tacrolimus therapy. Six databases were searched for studies on adult liver transplant recipients and donors of liver graft which reported tacrolimus dose requirement, trough blood concentration, and/or concentration/dose (C/D) ratio in expressers and nonexpressers of CYP3A5*1. Eligible data were pooled by meta-analysis. Sixteen observational studies (1309 recipients, 1044 donors of liver graft) were included in the analyses. Tacrolimus C/D ratio was lower, and the dose was higher in recipient expressers of CYP3A5*1 and/or carriers of expresser liver graft at 1-4 weeks and 2-4, 6, and 12 months post-transplantation. Tacrolimus blood concentration was lower at the first two weeks. Pair expressers were affected by about twofold, and the effect was different between ethnic groups. CYP3A5*1 expression in recipients increased tacrolimus required dose by 0.023 at first, 0.022 at third, and 0.012 mg/kg/day at sixth month. Its expression in graft tissue increased tacrolimus required dose by 0.024 at first, 0.035 at third, and 0.032 mg/kg/day at sixth month. Considering CYP3A5*1 polymorphism can be helpful in individualization of tacrolimus efficient dose prior to administration, and it can remove initial high-risk lag time (over/underdose period before reaching target blood level) at first few days post-transplantation.

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“…Concerning CNIs, tapering of tacrolimus may have a positive effect on glucose tolerance [ 169 , 170 ], but there are no trials directly aimed at assessing the influence of different CNI dosing regimens on glycemic control in PLTDM. A few trials have assessed metabolic outcomes after the change in treatment regimen from tacrolimus to cyclosporine, reporting notable benefits [ 171 , 172 ].…”

Section: Management Of Pltdmmentioning

confidence: 99%

Post-Liver Transplantation Diabetes Mellitus: A Review of Relevance and Approach to Treatment

et al. 2018

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Post-liver transplantation diabetes mellitus (PLTDM) develops in up to 30% of liver transplant recipients and is associated with increased risk of mortality and multiple morbid outcomes. PLTDM is a multicausal disorder, but the main risk factor is the use of immunosuppressive agents of the calcineurin inhibitor (CNI) family (tacrolimus and cyclosporine). Additional factors, such as pre-transplant overweight, nonalcoholic steatohepatitis and hepatitis C virus infection, may further increase risk of developing PLTDM. A diagnosis of PLTDM should be established only after doses of CNI and steroids are stable and the post-operative stress has been overcome. The predominant defect induced by CNI is insulin secretory dysfunction. Plasma glucose control must start immediately after the transplant procedure in order to improve long-term results for both patient and transplant. Among the better known antidiabetics, metformin and DPP-4 inhibitors have a particularly benign profile in the PLTDM context and are the preferred oral agents for long-term management. Insulin therapy is also an effective approach that addresses the prevailing pathophysiological defect of the disorder. There is still insufficient evidence about the impact of newer families of antidiabetics (GLP-1 agonists, SGLT-2 inhibitors) on PLTDM. In this review, we summarize current knowledge on the epidemiology, pathogenesis, course of disease and medical management of PLTDM.

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Benefits of minimizing immunosuppressive dosage according to cytochrome P450 3A5 genotype in liver transplant patients: findings from a single-center study

Cited by 7 publications

References 16 publications

Translational Knowledge Discovery Between Drug Interactions and Pharmacogenetics

Translational Knowledge Discovery Between Drug Interactions and Pharmacogenetics

Effect of CYP3A5*1 expression on tacrolimus required dose after liver transplantation: A systematic review and meta‐analysis

Post-Liver Transplantation Diabetes Mellitus: A Review of Relevance and Approach to Treatment

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