Effect of GSTA1 Variants on Busulfan-Based Conditioning Regimen Prior to Allogenic Hematopoietic Stem-Cell Transplantation in Pediatric Asians

• Published in: Pharmaceutics 2022-02, Vol.14 (2), p.401
• Main Authors: Nguyen, Ai-Hoc, Biswas, Mohitosh, Puangpetch, Apichaya, Prommas, Santirhat, Pakakasama, Samart, Anurathapan, Usanarat, Rachanakul, Jiratha, Sukprasong, Rattanaporn, Nuntharadtanaphong, Nutthan, Jongjitsook, Nutcha, Hongeng, Suradej, Sukasem, Chonlaphat
• Format: Article
• Language: English
• Subjects: Asian people; busulfan; Chemotherapy; Disease prevention; Drug dosages; Enzymes; GST genetic polymorphisms; hematopoietic stem-cell transplantation pharmacokinetics; Metabolism; Metabolites; Patients; pediatric Asians; Pediatrics; Pharmacokinetics; Population; White people
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics14020401

Busulfan is widely used as a chemotherapy treatment before hematopoietic stem-cell transplantation (HSCT). However, the response of busulfan is highly variable and unpredictable, whereby the pharmacogenetic interference of glutathione -transferase (GST) has strong evidence in Caucasians and some adult Asians but not in pediatric Asian patients. This study was aimed at investigating the associations of genetic polymorphisms with variations in the pharmacokinetic (PK) properties of busulfan in pediatric Asian patients. This retrospective cohort study recruited 92 pediatric patients. The polymorphism of was genotyped by Sanger sequencing, and and were genotyped by real-time PCR. Drug concentration and PK estimation were identified using an LC-MS/MS method and a noncompartmental model. Statistical analysis was performed by R software. Out of 92 patients, 48 (53%) were males, the mean age was 8.4 ± 5.12 years old, and the average weight was 26.52 ± 14.75 kg. The allele frequencies of and of and * deletions were 16.9%, 68.5%, and 21.2%, respectively. Patients with had a statistically significant impact on the PK of busulfan, whereas those with and did not ( > 0.05). The carriers of showed a significant difference compared to noncarriers in terms of t (for first dose: 161.9 vs. 134.3 min, = 0.0016; for second dose: 156.1 vs. 129.8, = 0.012), CL (88.74 vs. 124.23 mL/min, = 0.0089), C (4232.6 vs. 3675.5 ng/mL, = 0.0021), and AUC (5310.6 vs. 4177.1 µM/min, = 0.00033). The augmentation of AUC was around 27.1% in patients carrying the * variant. The polymorphism was significantly associated with variations of the pharmacokinetic properties of busulfan treatment in pediatric Asian patients.