ArticleEuropean journal of clinical pharmacology2014
The influence of CYP3A, PPARA, and POR genetic variants on the pharmacokinetics of tacrolimus and cyclosporine in renal transplant recipients.
Article in European journal of clinical pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 2 of them syntheses that pooled it.
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Who cites it
50 citing papers in PubMed, 2 syntheses or guidelines pooled it, 127 citations in OpenAlex.
- Effects of CYP3A4*22 and POR*28 variations on the pharmacokinetics of tacrolimus in renal transplant recipients: a meta-analysis of 18 observational studies.BMC nephrology · 2024Pooled it
- Effects ofFrontiers in pharmacology · 2023Pooled it
- Pharmacokinetics of Prolonged-Release Once-Daily Formulations of Tacrolimus in De Novo Kidney Transplant Recipients: A Randomized, Parallel-Group, Open-Label, Multicenter Study.Advances in therapy · 2019Trial
- Trial
- The effect of CYP3A4, CYP3A5 and MDR1 (ABCB1) single nucleotide polymorphisms on the pharmacokinetics of cyclosporine in Algerian stable renal transplant recipients.Molecular biology reports · 2025Article
- Composite CYP3A (CYP3A4 and CYP3A5) phenotypes and influence on tacrolimus dose adjusted concentrations in adult heart transplant recipients.The pharmacogenomics journal · 2024Article
- Pharmacogenetics of Calcineurin inhibitors in kidney transplant recipients: the African gap. A narrative review.Pharmacogenomics · 2024Review
- The effects of the CYP3A5*3 variant on tacrolimus pharmacokinetics and outcomes in Tunisian kidney transplant recipients.La Tunisie medicale · 2023Article
- Tacrolimus pharmacokinetics are influenced by CYP3A5, age, and concomitant fluconazole in pediatric kidney transplant patients.Clinical and translational science · 2023Article
- Initial dosage optimisation of cyclosporine in Chinese paediatric patients undergoing allogeneic haematopoietic stem cell transplantation based on population pharmacokinetics: a retrospective study.BMJ paediatrics open · 2023Article
- The Effect of Voriconazole on Tacrolimus in Kidney Transplantation Recipients: A Real-World Study.Pharmaceutics · 2022Article
- Insights into the Pharmacogenetics of Tacrolimus Pharmacokinetics and Pharmacodynamics.Pharmaceutics · 2022Review
- Use of Pharmacogenetics to Optimize Immunosuppressant Therapy in Kidney-Transplanted Patients.Biomedicines · 2022Review
- Association of P450 Oxidoreductase Gene Polymorphism with Tacrolimus Pharmacokinetics in Renal Transplant Recipients: A Systematic Review and Meta-Analysis.Pharmaceutics · 2022Review
- Prospective population pharmacokinetic study of tacrolimus in adult recipients early after liver transplantation: A comparison of Michaelis-Menten and theory-based pharmacokinetic models.Frontiers in pharmacology · 2022Article
- Evaluation of clinical and genetic factors in the population pharmacokinetics of carbamazepine.British journal of clinical pharmacology · 2021Article
- CYP3A5 and PPARA genetic variants are associated with low trough concentration to dose ratio of tacrolimus in kidney transplant recipients.European journal of clinical pharmacology · 2021Article
- Monitoring the tacrolimus concentration in peripheral blood mononuclear cells of kidney transplant recipients.British journal of clinical pharmacology · 2021Article
- Review
- Genetic Polymorphisms Affecting Tacrolimus Metabolism and the Relationship to Post-Transplant Outcomes in Kidney Transplant Recipients.Pharmacogenomics and personalized medicine · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTacrolimus (Tac) and cyclosporine (CsA) are mainly metabolized by CYP3A4 and CYP3A5. Several studies have demonstrated an association between the CYP3A5 genotype and Tac dose requirements. Recently, CYP3A4, PPARA, and POR gene variants have been shown to influence CYP3A metabolism. The present study investigated potential associations between CYP3A5*3, CYP3A4*22, PPARA c.209- 1003G>A and c.208+3819A>G, and POR*28 alleles and dose-adjusted concentrations (C/D) of Tac and CsA in 177 renal transplant patients early post-transplant.
methodsAll patients (n=177) were genotyped for CYP3A4*22, CYP3A5*3, POR*28, PPARA c.209-1003G>A, and PPARA c.208+3819A>G using real-time polymerase chain reaction (PCR) and melting curve analysis with allelespecific hybridization probes or PCR restriction fragment length polymorphisms (RFLP) methods. Drug concentrations and administered doses were retrospectively collected from patient charts at Oslo University Hospital, Rikshospitalet, Norway. One steady-state concentration was collected for each patient.
resultsWe confirmed a significant impact of the CYP3A5*3 allele on Tac exposure. Patients with POR*28 and PPARA variant alleles demonstrated 15 % lower (P=0.04) and 19 % higher (P=0.01) Tac C0/D respectively. CsA C2/D was 53 % higher among CYP3A4*22 carriers (P=0.03).
conclusionThe results support the use of pre-transplant CYP3A5 genotyping to improve initial dosing of Tac, and suggest that Tac dosing may be further individualized by additional POR and PPARA genotyping. Furthermore, initial CsA dosing may be improved by pre-transplant CYP3A4*22 determination.
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