ArticleBritish journal of clinical pharmacology2024
Steroid-tacrolimus drug-drug interaction and the effect of CYP3A genotypes.
Article in British journal of clinical pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- A Review of Population Pharmacokinetic Models and Dosing Algorithms Assessing the Influence of CYP3A5 Genotype and Other Clinical Covariates on Tacrolimus Pharmacokinetics.Clinical pharmacokinetics · 2026Review
- Precision Dosing of Tacrolimus in Liver Transplantation: Integrating Donor-Recipient CYP3A5 Pharmacogenomics and Drug Interactions.CPT: pharmacometrics & systems pharmacology · 2026Article
- Population pharmacokinetics of tacrolimus and CYP3A5-driven variability: implications for model-informed dose individualization in pediatric renal transplant recipients.BMC pharmacology & toxicology · 2026Article
- Lower Dose-Normalized Tacrolimus Exposure in CYP3A5*6 vs. *3 Loss-of-Function Allele Carriers: A Longitudinal Retrospective Real-World Study in Kidney Transplant Recipients.Clinical pharmacology and therapeutics · 2026Article
- Advancing Drug-Drug Interaction Prediction with Biomimetic Improvements: Leveraging the Latest Artificial Intelligence Techniques to Guide Researchers in the Field.Biomimetics (Basel, Switzerland) · 2026Review
- Machine learning driven precision medicine in tacrolimus dosing: current research and future perspectives in liver and kidney transplantation.Frontiers in immunology · 2026Review
- [Effect ofSichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025Article
- Drug-Drug Interactions and Individualized Clozapine Therapy in Patients with Depression: Insights from Real-World Data.Drug design, development and therapy · 2025Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
aimsTacrolimus, metabolized by CYP3A4 and CYP3A5 enzymes, is susceptible to drug-drug interactions (DDI). Steroids induce CYP3A genes to increase tacrolimus clearance, but the effect is variable. We hypothesized that the extent of the steroid-tacrolimus DDI differs by CYP3A4/5 genotypes.
methodsKidney transplant recipients (n = 2462) were classified by the number of loss of function alleles (LOF) (CYP3A5*3, *6 and *7 and CYP3A4*22) and steroid use at each tacrolimus trough in the first 6 months post-transplant. A population pharmacokinetic analysis was performed by nonlinear mixed-effect modelling (NONMEM) and stepwise covariate modelling to define significant covariates affecting tacrolimus clearance. A stochastic simulation was performed and translated into a Shiny application with the mrgsolve and Shiny packages in R.
resultsSteroids were associated with modestly higher (3%-11.8%) tacrolimus clearance. Patients with 0-LOF alleles receiving steroids showed the greatest increase (11.8%) in clearance compared to no steroids, whereas those with 2-LOFs had a negligible increase (2.6%) in the presence of steroids. Steroid use increased tacrolimus clearance by 5% and 10.3% in patients with 1-LOF and 3/4-LOFs, respectively.
conclusionsSteroids increase the clearance of tacrolimus but vary slightly by CYP3A genotype. This is important in individuals of African ancestry who are more likely to carry no LOF alleles, may more commonly receive steroid treatment, and will need higher tacrolimus doses.
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