ArticlePharmacotherapy2018
Tacrolimus Elimination in Four Patients With a CYP3A5*3/*3 CYP3A4*22/*22 Genotype Combination.
Article in Pharmacotherapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Effects ofFrontiers in pharmacology · 2023Pooled it
- Differences in Early Tacrolimus Exposure in Kidney Transplant Recipients With and Without CYP3A5 Genotype-Guided Tacrolimus Dosing.Clinical and translational science · 2026Article
- Utilization of Cannabidiol in Post-Organ-Transplant Care.International journal of molecular sciences · 2025Review
- Applications of the Cholesterol Metabolite, 4β-Hydroxycholesterol, as a Sensitive Endogenous Biomarker for Hepatic CYP3A Activity Evaluated within a PBPK Framework.Pharmaceutics · 2024Article
- Pharmacogenomics of Old and New Immunosuppressive Drugs for Precision Medicine in Kidney Transplantation.Journal of clinical medicine · 2023Review
- Article
- Interplay of Vitamin D and CYP3A4 Polymorphisms in Endocrine Disorders and Cancer.Endocrinology and metabolism (Seoul, Korea) · 2022Review
- Precision Dosing for Tacrolimus Using Genotypes and Clinical Factors in Kidney Transplant Recipients of European Ancestry.Journal of clinical pharmacology · 2021Observational
- Review
- Tacrolimus troughs and genetic determinants of metabolism in kidney transplant recipients: A comparison of four ancestry groups.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2019Observational
- A Theoretical Physiologically-Based Pharmacokinetic Approach to Ascertain Covariates Explaining the Large Interpatient Variability in Tacrolimus Disposition.CPT: pharmacometrics & systems pharmacology · 2019Article
- The Impact ofFrontiers in genetics · 2019Article
- Effect of CYP3A4 and PPARA polymorphism on concentration-to-dose ratio and adverse effects of tacrolimus in Pakistani liver transplant recipients.Pakistan journal of medical sciencesArticle
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Cytochrome P450 3A5 (CYP3A5) and cytochrome P450 3A4 (CYP3A4) are the predominate enzymes responsible for tacrolimus metabolism. The presence of CYP3A4 and CYP3A5 genetic variants significantly affects tacrolimus clearance and dose requirements. CYP3A5*3 is a loss-of-function variant resulting in no CYP3A5 enzyme production. CYP3A4*22 is a variant that reduces production of functional CYP3A4 protein. Caucasians commonly carry these variant alleles but are very rarely homozygous for both CYP3A5*3 and CYP3A4*22. This report describes four kidney transplant recipients who carry a rare genotype combination (CYP3A5*3/*3 and CYP3A4*22/*22). These patients were identified from a larger cohort of Caucasian kidney transplant recipients (n=1366). To understand the significance of this genotype combination on tacrolimus troughs and doses, we compared these patients to recipients without this combination. Patients homozygous for both variants are at risk for profound reductions in metabolism of CYP3A substrates. A 342% and a 90.6% increase in the median dose-normalized trough was observed, when the CYP3A5*3/*3 and CYP3A4*22/*22 genotype combination was compared to the CYP3A5*1/*1 and CYP3A4*1/*1 genotype combination and the CYP3A5*3/*3 and CYP3A4*1/*1 genotype combination, respectively. These four individuals only required on average 2.5 mg/day of tacrolimus. Knowledge of these genotypes would be useful in selecting appropriate tacrolimus doses to avoid overexposure.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.