Population pharmacokinetics and pharmacodynamics of busulfan with GSTA1 polymorphisms in patients undergoing allogeneic hematopoietic stem cell transplantation
- Authors
- Choi, Boyoon; Kim, Myeong Gyu; Han, Nayoung; Kim, Therasa; Ji, Eunhee; Park, Seonyang; Kim, In-Wha; Oh, Jung Mi
- Issue Date
- 2015
- Publisher
- FUTURE MEDICINE LTD
- Keywords
- allogeneic hematopoietic stem cell transplantation; alloHSCT; busulfan; clinical outcomes; genetic polymorphisms; glutathione s-transferase a1; GSTA1; population pharmacokinetics
- Citation
- PHARMACOGENOMICS, v.16, no.14, pp.1585 - 1594
- Journal Title
- PHARMACOGENOMICS
- Volume
- 16
- Number
- 14
- Start Page
- 1585
- End Page
- 1594
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/11841
- DOI
- 10.2217/pgs.15.98
- ISSN
- 1462-2416
- 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.
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