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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 <i>S</i>-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 <i>GST</i> 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 <i>GSTA1</i> was genotyped by Sanger sequencing, and <i>GSTM1</i> and <i>GSTP1</i> 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 <i>GSTA1*B</i> and of <i>GSTM1</i> and <i>GSTP1</i>* deletions were 16.9%, 68.5%, and 21.2%, respectively. Patients with <i>GSTA1*B</i> had a statistically significant impact on the PK of busulfan, whereas those with <i>GSTM1</i> and <i>GSTP1</i> did not (<i>p</i> > 0.05). The carriers of <i>GSTA1*B</i> showed a significant difference compared to noncarriers in terms of t_1/2 (for first dose: 161.9 vs. 134.3 min, <i>p</i> = 0.0016; for second dose: 156.1 vs. 129.8, <i>p</i> = 0.012), CL (88.74 vs. 124.23 mL/min, <i>p</i> = 0.0089), C_max (4232.6 vs. 3675.5 ng/mL, <i>p</i> = 0.0021), and AUC (5310.6 vs. 4177.1 µM/min, <i>p</i> = 0.00033). The augmentation of AUC was around 27.1% in patients carrying the <i>GSTA1</i>*<i>B</i> variant. The <i>GSTA1</i> polymorphism was significantly associated with variations of the pharmacokinetic properties of busulfan treatment in pediatric Asian patients.