ArticleEuropean journal of drug metabolism and pharmacokinetics2019
The Effects of CYP3A5 Genetic Polymorphisms on Serum Tacrolimus Dose-Adjusted Concentrations and Long-Term Prognosis in Chinese Heart Transplantation Recipients.
Article in European journal of drug metabolism and pharmacokinetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 12 citations in OpenAlex.
- Cohort Study to Determine the Impact of CYP3A5 Genotype on Tacrolimus Dosing Requirements and Trough Concentrations in Heart Transplant Recipients.Pharmacotherapy · 2026Article
- Initial Dosage Optimization of Tacrolimus in Connective Tissue Disease-Associated Interstitial Lung Disease Patients: An Exploratory Study.Drug design, development and therapy · 2026Article
- Association ofCurrent drug metabolism · 2024Article
- Optimizing the initial tacrolimus dosage in Chinese children with lung transplantation within normal hematocrit levels.Frontiers in pediatrics · 2024Article
- The impact of cytochrome P450 3A5 genotype on early tacrolimus metabolism and clinical outcomes in lung transplant recipients.International journal of clinical pharmacy · 2022Article
- Increased Incidence of Chronic Kidney Injury in African Americans Following Cardiac Transplantation.Journal of racial and ethnic health disparities · 2021Article
- Genetic analysis of pharmacogenomic VIP variants in the Wa population from Yunnan Province of China.BMC genomic data · 2021Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesEffective management of immunosuppressants is extemely important to improve prognosis of heart transplant recipients. We aim to investigate the effects of cytochrome P450 (CYP) 3A5 (rs776746) single nucleotide polymorphisms (SNPs) on serum tacrolimus concentrations/doses (C/Ds, ng/mL per mg/kg) and long-term prognosis in Chinese heart transplant recipients.
methodsWe detected the CYP3A5 SNPs of 203 consecutive Chinese heart transplant recipients between August 2005 and July 2012, and 55 of them who received tacrolimus-based immunosuppressive therapy were enrolled in this study. The tacrolimus C/Ds at 1, 3, 6, 12, 24 and 36 months after transplantation were routinely calculated. X-ray-guided endomyocardial biopsies (EMBs) were performed at 1, 3 and 6 months after heart transplantion to evaluate acute rejection degrees. All participants were then followed up annually until May 2018. The designed primary endpoint was all-cause mortality.
resultsIn 55 heart transplant recipients (43 males and 12 females), CYP3A5 non-expressors (CYP3A5*3/*3, n = 40) had significantly higher tacrolimus C/Ds than expressors (CYP3A5*1/*3, n = 15) at all time points (P < 0.001). Chi-squared test showed no significant differences in EMB-proven acute rejections between the two groups within 6 months after heart transplantion. The median follow-up period was 94.7 months, and eight patients died. Kaplan-Meier analysis showed CYP3A5 expressors tend to have higher mortality than non-expressors (20% vs 12.5%, log-rank: P = 0.314).
conclusionsCYP3A5 SNPs affect tacrolimus pharmacokinetics in Chinese heart transplant recipients, and non-expressors have higher tacrolimus C/Ds. In addition, expressors tend to have a worse long-term prognosis than non-expressors.
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