ArticleEuropean journal of clinical pharmacology2011
The interactions of age, genetics, and disease severity on tacrolimus dosing requirements after pediatric kidney and liver transplantation.
Article in European journal of clinical pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 3 of them syntheses that pooled it.
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Who cites it
30 citing papers in PubMed, 3 syntheses or guidelines pooled it, 71 citations in OpenAlex.
- Effects of CYP3A5 polymorphisms on tacrolimus pharmacokinetics in pediatric kidney transplantation: a systematic review and meta-analysis of observational studies.World journal of pediatrics : WJP · 2017Pooled it
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing.Clinical pharmacology and therapeutics · 2015Guideline
- Effect of CYP3A5*3 on kidney transplant recipients treated with tacrolimus: a systematic review and meta-analysis of observational studies.The pharmacogenomics journal · 2015Pooled it
- A Population Pharmacokinetic Model Does Not Predict the Optimal Starting Dose of Tacrolimus in Pediatric Renal Transplant Recipients in a Prospective Study: Lessons Learned and Model Improvement.Clinical pharmacokinetics · 2020Trial
- A published pharmacogenetic algorithm was poorly predictive of tacrolimus clearance in an independent cohort of renal transplant recipients.British journal of clinical pharmacology · 2013Trial
- Tacrolimus pharmacokinetics are influenced by CYP3A5, age, and concomitant fluconazole in pediatric kidney transplant patients.Clinical and translational science · 2023Article
- Development of a predictive nomogram for switching immunosuppressive drugs in pediatric liver transplant recipients.Frontiers in pediatrics · 2023Article
- The Impact of Pharmacogenetics on Pharmacokinetics and Pharmacodynamics in Neonates and Infants: A Systematic Review.Pharmacogenomics and personalized medicine · 2022Review
- Treatment optimization of maintenance immunosuppressive agents in pediatric renal transplant recipients.Expert opinion on drug metabolism & toxicology · 2021Review
- CYP3A5 and UGT1A9 Polymorphisms Influence Immunosuppressive Therapy in Pediatric Kidney Transplant Recipients.Frontiers in pharmacology · 2021Article
- Role of Tacrolimus C/D Ratio in the First Year After Pediatric Liver Transplantation.Frontiers in pediatrics · 2021Article
- Tacrolimus variability is associated with de novo donor-specific antibody development in pediatric renal transplant recipients.Pediatric nephrology (Berlin, Germany) · 2020Observational
- The potential impact of hematocrit correction on evaluation of tacrolimus target exposure in pediatric kidney transplant patients.Pediatric nephrology (Berlin, Germany) · 2019Article
- Dosage Optimization Based on Population Pharmacokinetic Analysis of Tacrolimus in Chinese Patients with Nephrotic Syndrome.Pharmaceutical research · 2019Article
- The Ontogeny of UDP-glucuronosyltransferase Enzymes, Recommendations for Future Profiling Studies and Application Through Physiologically Based Pharmacokinetic Modelling.Clinical pharmacokinetics · 2019Review
- Clinical aspects of tacrolimus use in paediatric renal transplant recipients.Pediatric nephrology (Berlin, Germany) · 2019Review
- Tacrolimus Granules for Oral Suspension as Post-Transplant Immunosuppression in Routine Medical Practice in France: The OPTIMOD Study.Annals of transplantation · 2018Observational
- A Population Pharmacokinetic Model to Predict the Individual Starting Dose of Tacrolimus Following Pediatric Renal Transplantation.Clinical pharmacokinetics · 2018Article
- Tacrolimus dose requirements in paediatric renal allograft recipients are characterized by a biphasic course determined by age and bone maturation.British journal of clinical pharmacology · 2017Article
- The Effect of Weight and CYP3A5 Genotype on the Population Pharmacokinetics of Tacrolimus in Stable Paediatric Renal Transplant Recipients.Clinical pharmacokinetics · 2016Article
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Authors and funding
9 authors at 6 institutions in 3 countries.
Funding
Abstract
purposeIn children, data on the combined impact of age, genotype, and disease severity on tacrolimus (TAC) disposition are scarce. The aim of this study was to evaluate the effect of these covariates on tacrolimus dose requirements in the immediate post-transplant period in pediatric kidney and liver recipients.
methodsData were retrospectively collected describing tacrolimus disposition, age, CYP3A5 and ABCB1 genotype, and pediatric risk of mortality (PRISM) scores for up to 14 days post-transplant in children receiving liver and renal transplants. Initial TAC dosing was equal in all patients and adjusted using therapeutic drug monitoring. We determined the relationship between covariates and tacrolimus disposition.
resultsForty-eight kidney and 42 liver transplant recipients (median ages 11.5 and 1.5 years, ranges 1.5-17.7 and 0.05-14.8 years, respectively) received TAC post-transplant. In both transplant groups, younger children (<5 years) needed higher TAC doses than older children [kidney: 0.15 (0.07-0.35) vs. 0.09 (0.02-0.20) mg/kg/12h, p = 0.046, liver: 0.12 (0.04-0.32) vs. 0.09 (0.01-0.18) mg/kg/12h, p = 0.038]. In kidney but not liver transplants, CYP3A5 expressors needed significantly higher TAC doses than nonexpressors [0.15 (0.07-0.20) vs. 0.09 (0.02-0.35) mg/kg/12h, P = 0.001]. In these patients, age and CYP3A5 genotype were independently associated with TAC dosing requirement. In liver, but not kidney transplant patients, homozygous ABCB1 T-T-T haplotype carriers needed higher TAC doses than noncarriers [0.26 (0.15-0.32) vs. 0.11 (0.01-0.25) mg/kg/12h, p = 0.013].
conclusionCYP3A5 genotype may explain variation in tacrolimus disposition early after transplant in pediatric kidney recipients, independent of age-related variation. In contrast, in pediatric liver recipients, variation in tacrolimus disposition appears related to age and ABCB1 genotype. These findings illustrate the importance of the interplay among age, genotype, and transplant organ on tacrolimus disposition.
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