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

doi:10.2217/pgs.15.98

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

Department of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

32 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 language	English
Pages (from-to)	1585-1594
Number of pages	10
Journal	Pharmacogenomics
Volume	16
Issue number	14
DOIs	https://doi.org/10.2217/pgs.15.98
State	Published - Sep 2015

Bibliographical note

Publisher Copyright:
© 2015 Future Medicine Ltd.

Keywords

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

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

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.",

keywords = "GSTA1, alloHSCT, allogeneic hematopoietic stem cell transplantation, busulfan, clinical outcomes, genetic polymorphisms, glutathione s-transferase a1, population pharmacokinetics",

author = "Boyoon Choi and Kim, {Myeong Gyu} and Nayoung Han and Therasa Kim and Eunhee Ji and Seonyang Park and Kim, {In Wha} and Oh, {Jung Mi}",

note = "Publisher Copyright: {\textcopyright} 2015 Future Medicine Ltd.",

year = "2015",

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doi = "10.2217/pgs.15.98",

language = "English",

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T1 - Population pharmacokinetics and pharmacodynamics of busulfan with GSTA1 polymorphisms in patients undergoing allogeneic hematopoietic stem cell transplantation

AU - Choi, Boyoon

AU - Kim, Myeong Gyu

AU - Han, Nayoung

AU - Kim, Therasa

AU - Ji, Eunhee

AU - Park, Seonyang

AU - Kim, In Wha

AU - Oh, Jung Mi

PY - 2015/9

Y1 - 2015/9

N2 - 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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KW - GSTA1

KW - alloHSCT

KW - allogeneic hematopoietic stem cell transplantation

KW - busulfan

KW - clinical outcomes

KW - genetic polymorphisms

KW - glutathione s-transferase a1

KW - population pharmacokinetics

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ER -

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

Abstract

Bibliographical note

Keywords

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