Population pharmacokinetics and pharmacodynamics of busulfan with GSTA1 polymorphisms in patients undergoing allogeneic hematopoietic stem cell transplantation

Boyoon Choi, Myeong Gyu Kim, Nayoung Han, Therasa Kim, Eunhee Ji, Seonyang Park, In Wha Kim, Jung Mi Oh

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Aim: A population pharmacokinetic (PPK) analysis was conducted to describe the influence of GSTA1 polymorphisms on intravenous busulfan in adults undergoing allogeneic hematopoietic stem cell transplantation. Patients & methods: A PPK model was developed from 36 patients by a one-compartment model with first-order elimination. Results: The typical value of clearance and volume of distribution were 11.0 l/h and 42.4 l, respectively. Clearance decreased by 15% and area under the concentration-time curves (AUCs) increased with GSTA1 variants compared with wild-type (both p < 0.05). Subtherapeutic AUCs were seen only in wild-type patients. Conclusion: To our knowledge, this is the first PPK study to suggest that GSTA1 polymorphisms in adults are associated with busulfan PK.

Original languageEnglish
Pages (from-to)1585-1594
Number of pages10
JournalPharmacogenomics
Volume16
Issue number14
DOIs
StatePublished - Sep 2015

Keywords

  • GSTA1
  • alloHSCT
  • allogeneic hematopoietic stem cell transplantation
  • busulfan
  • clinical outcomes
  • genetic polymorphisms
  • glutathione s-transferase a1
  • population pharmacokinetics

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