ArticleClinical and translational science2023
Tacrolimus pharmacokinetics are influenced by CYP3A5, age, and concomitant fluconazole in pediatric kidney transplant patients.
Article in Clinical and translational science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 9 citations in OpenAlex.
- 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
- The case for combined pediatric nephrology and clinical pharmacology training.Pediatric nephrology (Berlin, Germany) · 2026Article
- Localized Tacrolimus Delivery for Peripheral Nerve Regeneration: Molecular Mechanisms, Biomaterial Platforms, and Translational Strategies.International journal of molecular sciences · 2026Review
- Cohort Study to Determine the Impact of CYP3A5 Genotype on Tacrolimus Dosing Requirements and Trough Concentrations in Heart Transplant Recipients.Pharmacotherapy · 2026Article
- The Impact of CYP3A5 Genotype on Tacrolimus Pharmacokinetics in Children following Heart Transplant.Research square · 2026Article
- Model Informed Precision Dosing of Tacrolimus in Children Following Heart Transplant.Journal of clinical pharmacology · 2026Article
- Tacrolimus Pharmacokinetics in Pediatric Liver Transplant Recipients During the First Month After Transplantation.European journal of drug metabolism and pharmacokinetics · 2026Article
- Translating real-world evidence/real-world data.Clinical and translational science · 2024Article
- Safety of fluconazole in kidney transplant recipients for prevention of coccidioidomycosis.Medical mycology · 2024Article
- Tacrolimus pharmacokinetics are influenced by CYP3A5, age, and concomitant fluconazole in pediatric kidney transplant patients.Clinical and translational science · 2023Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Tacrolimus, the most common immunosuppressant for organ transplant, has a narrow therapeutic range and is metabolized by CYP3A4/5. Trough concentration monitoring and dosing adjustments are used to reach a therapeutic range. CYP3A5 intermediate and normal metabolizers (*1 allele carriers; IM/NM) demonstrate faster tacrolimus metabolism than poor metabolizers (PM). We analyzed the electronic health records of 93 patients aged <21 years for the first 8 weeks after a kidney transplant between January 2010 and December 2021. The target tacrolimus trough was 10-15 ng/mL in the first 4 weeks and 7-10 ng/mL in the next 4 weeks. Banked DNA was collected and genotyped for CYP3A5*3, *6, *7, and *8 alleles. We found that CYP3A5 IM/NM (n = 21) took longer than PM (n = 72) to reach the therapeutic range (7 vs. 4 days, p = 0.048). IM/NM had more dose adjustments (8 vs. 6, p = 0.025) and needed >150% of the required daily dose compared with PM. The concentration/dose ratio was influenced by age and concomitant fluconazole (p = 0.0003, p = 0.034, respectively) and the average daily dose decreases with age in CYP3A5 PM (p = 0.001). Tremors were more common in patients who ever had a trough concentration >15 ng/mL compared with those who never had a trough concentration >15 ng/mL (OR 3.31, 95% CI 1.03-8.98, p = 0.038). Using standard dosing, CYP3A5 IM/NM took longer to reach the goal range and require more dose adjustments and higher doses than PM. Preemptive genotyping could decrease the number of dose changes necessary to reach a therapeutic dose. We have implemented pre-transplant CYP3A5 testing at our institution.
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