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

Background 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 pe...

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Veröffentlicht in:	Pediatric nephrology (Berlin, West) West), 2014-10, Vol.29 (10), p.2039-2049
Hauptverfasser:	Lalan, Shwetal, Abdel-Rahman, Susan, Gaedigk, Andrea, Leeder, J. Steven, Warady, Bradley A., Dai, Hongying, Blowey, Douglas
Format:	Artikel
Sprache:	eng
Schlagworte:	Adolescent Adrenal Cortex Hormones - therapeutic use Age Age Factors Anti-Infective Agents, Local - therapeutic use Child Child, Preschool Clotrimazole - therapeutic use Cytochrome Cytochrome P-450 CYP3A - genetics Dosage and administration Drug dosages Drug therapy Enzymes Female Genotype Genotype & phenotype Humans Immunosuppressive Agents - blood Immunosuppressive Agents - therapeutic use Infant Influence Kidney failure Kidney Transplantation Kidney transplants Kidneys Male Medicine Medicine & Public Health Metabolism Nephrology Original Article Patients Pediatrics Polymorphism, Single Nucleotide Retrospective Studies Steroids Tacrolimus Tacrolimus - blood Tacrolimus - therapeutic use Toxicity Transplantation Urology Young Adult
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Zusammenfassung:	Background 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. Methods Data were collected retrospectively for the first year post-transplant in pediatric renal transplant patients receiving TAC maintenance immunosuppression. The effect of CYP3A5 genotype ( CYP3A53 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. Results Over time, TAC Co/D was lower in recipients with CYP3A51/3 genotype compared to those with CYP3A53/3 genotype (44.5 ± 14.4 vs. 107.6 ± 6.4, p = 0.03), increased in patients >12 years of age compared to
ISSN:	0931-041X 1432-198X
DOI:	10.1007/s00467-014-2827-2