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Effect of CYP3A5 genotype, steroids, and azoles on tacrolimus in a pediatric renal transplant population



Numerous studies have described the impact of cytochrome P450 3A5 (CYP3A5) genotype on Tacrolimus (TAC) exposure. The purpose of this study was to conduct a comprehensive analysis of genetic and non-genetic factors affecting the TAC dose–exposure relationship over the first year post pediatric renal transplant.


Data were collected retrospectively for the first year post-transplant in pediatric renal transplant patients receiving TAC maintenance immunosuppression. The effect of CYP3A5 genotype (CYP3A5*3 and *6 alleles), age, azoles, and corticosteroids on TAC trough concentration normalized for dose (TAC Co/D ng/ml/mg/kg/day) was assessed using a linear mixed model.


Over time, TAC Co/D was lower in recipients with CYP3A5*1/*3 genotype compared to those with CYP3A5*3/*3 genotype (44.5 ± 14.4 vs. 107.6 ± 6.4, p = 0.03), increased in patients >12 years of age compared to < 12 years (93.9 ± 8.7 vs. 53.1 ± 12.9, p = 0.007), and decreased by concomitant corticosteroids (69.5 ± 12.7 vs. 89.9 ± 20.0, p = 0.04). The observed increased TAC Co/D in the presence of azoles (271 ± 41 vs. 111 ± 91, p = 0.016) could be attributed to clotrimazole.


Multiple factors, including CYP3A5 genotype, and age, influence TAC Co/D in pediatric kidney transplant recipients. Clotrimazole administered as troches also contribute to TAC Co/D variability.

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CYP3A5 :

Cytochrome P450 3A5




TAC exposure normalized for dose


Therapeutic drug monitoring


Mycophenolate mofetil


Chronic allograft nephropathy


Basic metabolic panel


Complete blood count


Estimated glomerular filtration rate




Linear mixed model


Liquid chromatography-tandem mass spectrometry


Standard deviation


ATP-Binding Cassette, Sub-Family B1 drug transporter gene: also known as MDR1)


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Correspondence to Shwetal Lalan.

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Lalan, S., Abdel-Rahman, S., Gaedigk, A. et al. Effect of CYP3A5 genotype, steroids, and azoles on tacrolimus in a pediatric renal transplant population. Pediatr Nephrol 29, 2039–2049 (2014).

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  • Pharmacogenetics
  • CYP3A5
  • Fluconazole
  • Clotrimazole
  • Renal transplant
  • Tacrolimus
  • Children