Objective To explore the association between glutathione S-transferase (GST) M1 and T1 genetic polymorphisms and the blood methotrexate concentration at 48 hours (C4s h) after initiation of high-dose methotrexate (HDMTX) infusion and major adverse events within 72 hours in children with acute lymphoblastic leukemia (ALL).Methods Medical records of ALL children in the First Affiliated Hospital of Xiamen University who received HDMTX-containing chemotherapy regimen,blood concentration monitoring of methotrexate at 48 hours after initiation of infusion,and GST M1 and T1 genetic polymorphism detection were collected and retrospectively analyzed.Results A total of 94 children with ALL were enrolled in the study,including 52 males and 42 females,aged 2-15 years with the average age of (5 ± 3) years.Within 72 hours after the HDMTX chemotherapy,44 children (46.8％) developed liver injury,43 children (45.7％) developed gastrointestinal reactions,15 children (16.0％) developed myelosuppression,and 45 children (47.9％) developed skin and mucosa injury.The children were divided into the ＜0.5 μmol/L group,the 0.5-1.0 μmol/L group,and the ＞ 1.0 μmol/L group according to their C48h of methotrexate.The incidences of adverse events such as liver injury,gastrointestinal reaction,and skin and mucosa injury in the ＜0.5 μmol/L group were significantly lower than those in the ＞ 1.0 μmol/L group [17.9％ (5/28) vs.78.6％ (11/14),21.4％ (6/28)vs.85.7％ (12/14),17.9％ (5/28)vs.71.4％ (10/14),all P＜0.001].Significant differences of methotrexate C48 h/dose ratio were found neither between children with functional wild-type alleles of GST M1 (GST M1 non-null genotypes) and those with GST M1 null-genotypes nor between children with GST T1 non-null genotypes and those with GST T1 null genotypes (both P ＞0.05).But the incidences of liver injury within 72 hours after HDMTX chemotherapy in children with GST M1 and GST T1 null-genotypes were significantly higher than those in children with GST M1 and GST T1 non-null genotypes,respectively [GST M1:50.7％ (36/71) vs.34.8％ (8/23);GST T1:55.2％ (32/58) vs.33.3％ (12/36),both P ＜0.05].Multivariate logistic regression analysis showed that GST M1 and GST T1 genetic polymorphisms were associated with increased risk of liver injury (OR =1.928,95％CI:1.353-2.745,P＜0.001;OR =2.462,95％CI:1.046-5.793,P=0.039).Conclusions The C48 h of methotrexate in children with ALL and receiving HDMTX chemotherapy was associated with the occurrence of adverse events.GST M1 and GST T1 genetic polymorphisms had no significant effects on C48 h of methotrexate,but might increase the risk of liver injury in children.

Objective To explore the association between glutathione S-transferase (GST) M1 and T1 genetic polymorphisms and the blood methotrexate concentration at 48 hours (C4s h) after initiation of high-dose methotrexate (HDMTX) infusion and major adverse events within 72 hours in children with acute lymphoblastic leukemia (ALL).Methods Medical records of ALL children in the First Affiliated Hospital of Xiamen University who received HDMTX-containing chemotherapy regimen,blood concentration monitoring of methotrexate at 48 hours after initiation of infusion,and GST M1 and T1 genetic polymorphism detection were collected and retrospectively analyzed.Results A total of 94 children with ALL were enrolled in the study,including 52 males and 42 females,aged 2-15 years with the average age of (5 ± 3) years.Within 72 hours after the HDMTX chemotherapy,44 children (46.8％) developed liver injury,43 children (45.7％) developed gastrointestinal reactions,15 children (16.0％) developed myelosuppression,and 45 children (47.9％) developed skin and mucosa injury.The children were divided into the ＜0.5 μmol/L group,the 0.5-1.0 μmol/L group,and the ＞ 1.0 μmol/L group according to their C48h of methotrexate.The incidences of adverse events such as liver injury,gastrointestinal reaction,and skin and mucosa injury in the ＜0.5 μmol/L group were significantly lower than those in the ＞ 1.0 μmol/L group [17.9％ (5/28) vs.78.6％ (11/14),21.4％ (6/28)vs.85.7％ (12/14),17.9％ (5/28)vs.71.4％ (10/14),all P＜0.001].Significant differences of methotrexate C48 h/dose ratio were found neither between children with functional wild-type alleles of GST M1 (GST M1 non-null genotypes) and those with GST M1 null-genotypes nor between children with GST T1 non-null genotypes and those with GST T1 null genotypes (both P ＞0.05).But the incidences of liver injury within 72 hours after HDMTX chemotherapy in children with GST M1 and GST T1 null-genotypes were significantly higher than those in children with GST M1 and GST T1 non-null genotypes,respectively [GST M1:50.7％ (36/71) vs.34.8％ (8/23);GST T1:55.2％ (32/58) vs.33.3％ (12/36),both P ＜0.05].Multivariate logistic regression analysis showed that GST M1 and GST T1 genetic polymorphisms were associated with increased risk of liver injury (OR =1.928,95％CI:1.353-2.745,P＜0.001;OR =2.462,95％CI:1.046-5.793,P=0.039).Conclusions The C48 h of methotrexate in children with ALL and receiving HDMTX chemotherapy was associated with the occurrence of adverse events.GST M1 and GST T1 genetic polymorphisms had no significant effects on C48 h of methotrexate,but might increase the risk of liver injury in children.

Objective In order to provide a reference for optimizing the dosage regimen of carbamazepine and valproate in pediatric epilepsy patients .Methods Pharmacist consulted one pediatric epilepsy patient with traumatic brain injury for post operation epilepsy treatments .The abnormal plasma concentration of carbamazepine and valproic acid was analyzed with the population pharmacokinetic (PPK) model built by this team .New medication regimen was proposed and the predictive capabili-ty of this model was evaluated .Results Seizures in this patient have been effectively controlled .Conclusion Pharmacist can optimize the antiepileptic drug treatment with PPK model and achieve rational drug use clinically .

Objective To explore the correlation between aspirin resistance and COX-1, P2Y1, GPIa and GPIIIa gene polymorphism. Methods 35 case with aspirin resistant were selected and were given aspirin enteric coated tablets for oral treatment, 14 days.After the determination COX-1, P2Y1 and GPIa and GpIIIa gene polymorphism of each patient were analysis.Results The genotype AA of COX1 (A-842G) locus and CC of COX1 (C50T) locus was higher than other genotype (P<0.05);AG of P2Y1 (A1622G) locus genotype and CC of P2Y1 (C893T) locus genotype was higher than other genotype (P<0.05);CT of GPIa (C807T) locus genotype and GA of GPIa (G873A) locus genotype was higher than other genotype (P<0.05);PLA1/A1 of GPⅢa(T1565C)locus genotype was higher than other genotype (P<0.05).Conclusion P2Y1 (C893T), GPIa (C807T) allele is associated with aspirin resistance,With COX-1 (A-842G, C50T), GPIa (G873A), GP III A (T1565C), P2Y1 (A1622G) allele is more likely to induce the occurrence of aspirin resistance.