Association between CYP3A4, CYP3A5 and ABCB1 genotype and tacrolimus treatment outcomes among allogeneic HSCT patients

Pharmacogenomics. 2024 Jan;25(1):29-40. doi: 10.2217/pgs-2023-0204. Epub 2024 Jan 8.

Abstract

Aim: Successful treatment with tacrolimus to prevent graft versus host disease (GVHD) and minimize tacrolimus-related toxicities among allogeneic hematopoietic cell transplantation (alloHCT) recipients is contingent upon quickly achieving and maintaining concentrations within a narrow therapeutic range. The primary objective was to investigate associations between CYP3A4, CYP3A5 or ABCB1 genotype and the proportion of patients that attained an initial tacrolimus goal concentration following initiation of intravenous (iv.) and conversion to oral administration. Materials & methods: We retrospectively evaluated 86 patients who underwent HLA-matched (8/8) related donor alloHCT and were prescribed a tacrolimus-based regimen for GVHD prophylaxis. Results & conclusion: The findings of the present study suggests that CYP3A5 genotype may impact attainment of initial therapeutic tacrolimus concentrations with oral administration in alloHCT recipients.

Keywords: ABCB1; CYP3A4; CYP3A5; GVHD; pharmacogenetics; pharmacogenomics; tacrolimus.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • Cytochrome P-450 CYP3A / genetics
  • Cytochrome P-450 CYP3A / metabolism
  • Genotype
  • Graft vs Host Disease* / drug therapy
  • Graft vs Host Disease* / genetics
  • Graft vs Host Disease* / prevention & control
  • Hematopoietic Stem Cell Transplantation* / methods
  • Humans
  • Immunosuppressive Agents
  • Retrospective Studies
  • Tacrolimus
  • Treatment Outcome

Substances

  • Tacrolimus
  • Cytochrome P-450 CYP3A
  • Immunosuppressive Agents
  • CYP3A5 protein, human
  • CYP3A4 protein, human
  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B