Impact of CYP3A5 genotype on tacrolimus pharmacokinetics and clinical outcomes in pediatric patients with Henoch–Schönlein purpura nephritis

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AIM: This study aimed to evaluate the impact of CYP3A5 gene polymorphism on the pharmacokinetics, therapeutic efficacy, and safety of tacrolimus in pediatric patients with Henoch-Schönlein purpura nephritis (HSPN). METHODS: This study used a retrospective observational design to investigate pediatric patients with HSPN treated with tacrolimus. The polymorphism at the CYP3A5 was detected using PCR technology. The concentration of tacrolimus was quantitatively determined by ultra-performance liquid chromatography. The study systematically analyzed the impact of CYP3A5 gene polymorphism on the pharmacokinetic parameters of tacrolimus (including trough concentration C0, dose D, and dose-corrected concentration C0/D), clinical efficacy, and adverse reactions. RESULTS: The study enrolled 103 pediatric patients. Comparative analysis revealed that patients with CYP3A5*1/*1 or *1/*3 genotypes exhibited significantly lower tacrolimus C0 and C0/D at various time points when compared with CYP3A5*3/*3 genotype carriers. Furthermore, CYP3A5*1 expressers (CYP3A5*1/*1 and *1/*3) demonstrated markedly reduced tacrolimus C0 and C0/D levels across multiple time points relative to CYP3A5*3 nonexpressers (CYP3A5*3/*3). However, CYP3A5 genetic polymorphisms did not demonstrate significant associations with clinical efficacy or adverse reactions. CONCLUSION: The polymorphism of the CYP3A5 gene may provide information on the pharmacokinetics of tacrolimus in pediatric with HSPN, but its clinical relevance has not yet been demonstrated.

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