Population pharmacokinetics and pharmacodynamics of busulfan with GSTA1 polymorphisms in patients undergoing allogeneic hematopoietic stem cell transplantation. (September 2015)

• Record Type: Journal Article
• Authors: Choi, Boyoon; Kim, Myeong Gyu; Han, Nayoung; Kim, Therasa; Ji, Eunhee; Park, Seonyang; Kim, In-Wha; Oh, Jung Mi
• Is Part Of: Pharmacogenomics. Volume 16:Number 14(2015)
• Page Start: 1585
• Page End: 1594
• Publication Date: 2015-09
• Subjects: allogeneic hematopoietic stem cell transplantation -- alloHSCT -- busulfan -- clinical outcomes -- genetic polymorphisms -- glutathione s-transferase a1 -- GSTA1 -- population pharmacokinetics; Pharmacogenomics -- Periodicals; 615.1
• DOI: 10.2217/pgs.15.98
• Languages: English
• ISSNs: 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.