| Summary: | Single nucleotide polymorphisms in drug-metabolizing genes may affect tacrolimus pharmacokinetics. Here, we investigated the influence of genotypes of <i>CYP3A5</i>, <i>CYP2C19</i>, and <i>POR</i> on the concentration/dose (C/D) ratio of tacrolimus and episodes of acute graft-versus-host disease (GVHD) in Japanese recipients of allogeneic hematopoietic stem cell transplantation (HSCT). Thirty-six patients receiving the first HSCT using tacrolimus-based GVHD prophylaxis were enrolled with written informed consent. During continuous intravenous infusion, HSCT recipients carrying the <i>CYP3A5*1</i> allele, particularly those with at least one <i>POR*28</i> allele, had a significantly lower tacrolimus C/D ratio throughout all three post-HSCT weeks compared to that in recipients with <i>POR*1/*1</i> (<i>p</i> < 0.05). The <i>CYP3A5*3/*3</i> genotype and the concomitant use of voriconazole were independent predictors of an increased tacrolimus C/D ratio during the switch from continuous intravenous infusion to oral administration (<i>p</i> < 0.05). In recipients receiving concomitant administration of voriconazole, our results suggest an impact of not only <i>CYP3A5</i> and <i>CYP2C19</i> genotypes, but also plasma voriconazole concentration. Although switching from intravenous to oral administration at a ratio of 1:5 was seemingly appropriate in recipients with <i>CYP3A5*1</i>, a lower conversion ratio (1:2–3) was appropriate in recipients with <i>CYP3A5*3/*3</i>. Our results suggest that <i>CYP3A5</i>, <i>POR</i>, and <i>CYP2C19</i> polymorphisms are useful biomarkers for individualized dosage adjustment of tacrolimus in HSCT recipients.
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