ArticleBritish journal of clinical pharmacology2015
Personalizing initial calcineurin inhibitor dosing by adjusting to donor CYP3A-status in liver transplant patients.
Article in British journal of clinical pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 30 citations in OpenAlex.
- Trends in Precision Medicine and Pharmacogenetics as an Adjuvant in Establishing a Correct Immunosuppressive Therapy for Kidney Transplant: An Up-to-Date Historical Overview.International journal of molecular sciences · 2025Review
- Clinical significance and gene prediction of a novel classification system based on tacrolimus concentration-to-dose ratio in the early post-liver transplant period.Frontiers in pharmacology · 2025Article
- CPMKG: a condition-based knowledge graph for precision medicine.Database : the journal of biological databases and curation · 2024Article
- CYP3A-status is associated with blood concentration and dose-requirement of tacrolimus in heart transplant recipients.Scientific reports · 2021Article
- End-stage renal disease reduces the expression of drug-metabolizing cytochrome P450s.Pharmacological reports : PR · 2020Article
- Phenoconversion of CYP2D6 by inhibitors modifies aripiprazole exposure.European archives of psychiatry and clinical neuroscience · 2020Article
- Donor CYP3A5 genotype influences tacrolimus disposition on the first day after paediatric liver transplantation.British journal of clinical pharmacology · 2017Article
- Effect of diurnal variation, CYP2B6 genotype and age on the pharmacokinetics of nevirapine in African children.The Journal of antimicrobial chemotherapy · 2017Article
- Population Pharmacokinetic Modelling and Bayesian Estimation of Tacrolimus Exposure: Is this Clinically Useful for Dosage Prediction Yet?Clinical pharmacokinetics · 2016Review
- Economic Evaluation of Pharmacogenetic Tests in Patients Subjected to Renal Transplantation: A Review of Literature.Frontiers in public health · 2016Review
- Personalizing initial calcineurin inhibitor dosing by adjusting to donor CYP3A-status in liver transplant patients.British journal of clinical pharmacology · 2015Article
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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
aimsInter-individual variability in dose requirements of calcineurin inhibitors (CNI) has been linked to genetic polymorphisms of CYP3A enzymes. CYP3A5*3, CYP3A4*1B and CYP3A4*22 alleles of liver grafts may explain about one third of the inter-individual differences in pharmacokinetics of ciclosporin and tacrolimus in recipients. However, non-genetic factors, influencing CYP3A expression, can contribute to the variability of CYP3A function due to phenoconversion. The present study evaluated the association between CYP3A4 expression combined with CYP3A5 genotype of donor livers and recipients' CNI therapy after transplantation.
methodsThe contribution of donors' CYP3A5 genotype and CYP3A4 expression to the blood concentrations and dose requirements of CNIs was evaluated in 131 liver transplant recipients.
resultsThe recipients with grafts from normal CYP3A4 expresser donors carrying CYP3A5*3/*3 required CNI maintenance doses more or less similar to the bodyweight-controlled starting doses (9.1 mg kg(-1) of ciclosporin and 0.1 mg kg(-1) of tacrolimus). The patients transplanted with grafts from low CYP3A4 expressers required substantial reduction (by about 50%, 4.2 mg kg(-1) of ciclosporin, 0.047 mg kg(-1) of tacrolimus, P < 0.001), while the recipients with grafts from high expressers or with grafts carrying at least one copy of the functional CYP3A5*1 allele required an increase (by about 50% [12.8-13.8 mg kg(-1)] for ciclosporin and 100% [0.21 mg kg(-1) ] for tacrolimus, P < 0.001) of the initial CNI dose for achieving target blood concentrations.
conclusionsDonor livers' CYP3A-status, taking both CYP3A5 allelic variations and CYP3A4 expression into account, can better identify the risk of CNI over- or underexposure, and may contribute to the avoidance of misdosing-induced graft injury in the early post-operative period.
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