A randomized clinical trial of age and genotype-guided tacrolimus dosing after pediatric solid organ transplantation

Sandar Min, Tanya Papaz, Myriam Lafreniere-Roula, Nadya Nalli, Hartmut Grasemann, Steven M. Schwartz, Binita M. Kamath, Vicky Ng, Rulan S. Parekh, Cedric Manlhiot, Seema Mital

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Background: Tacrolimus pharmacokinetics are influenced by age and CYP3A5 genotype with CYP3A5 expressors (CYP3A5*1/*1 or *1/*3) being fast metabolizers. However, the benefit of genotype-guided dosing in pediatric solid organ transplantation has been understudied. Objective: To determine whether age and CYP3A5 genotype-guided starting dose of tacrolimus result in earlier attainment of therapeutic drug concentrations. Setting: Single hospital-based transplant center. Methods: This was a randomized, semi-blinded, 30-day pilot trial. Between 2012 and 2016, pediatric patients listed for solid organ transplant were consented and enrolled into the study. Participants were categorized as expressors, CYP3A5*1/*1 or CYP3A5*1/*3, and nonexpressors, CYP3A5*3/*3. Patients were stratified by age (≤ or > 6 years) and randomized (2:1) after transplant to receive genotype-guided (n = 35) or standard (n = 18) starting dose of tacrolimus for 36-48 hours and were followed for 30 days. Results: Median age at transplant in the randomized cohort was 2.1 (0.75-8.0) years; 24 (45%) were male. Participants in the genotype-guided arm achieved therapeutic concentrations earlier at a median (IQR) of 3.4 (2.5-6.6) days compared to those in the standard dosing arm of 4.7 (3.5-8.6) days (P = 0.049), and had fewer out-of-range concentrations [OR (95% CI) = 0.60 (0.44, 0.83), P = 0.002] compared to standard dosing, with no difference in frequency of adverse events between the two groups. Conclusions: CYP3A5 genotype-guided dosing stratified by age resulted in earlier attainment of therapeutic tacrolimus concentrations and fewer out-of-range concentrations.

Original languageEnglish (US)
Article numbere13285
JournalPediatric transplantation
Issue number7
StatePublished - Nov 2018
Externally publishedYes


  • genetics
  • immunosuppression
  • pediatric transplantation
  • solid organ
  • tacrolimus
  • therapeutic drug monitoring
  • transplantation

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Transplantation


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