Abstract：OBJECTIVE: Cytochrome P450 3A4(CYP3A4) is involved in the metabolisms of many environmental toxins as well as over 50% of drugs including commonly used chemotherapeutic drugs. Polymorphism studies have demonstrated that there are significant individual variations in CYP3A4 activity as well as various distributions in different ethnicities and diseases. Currently there was no reported method in the large scale analysis of CYP3A4 activity. This study aimed to develop a simple, stable and reliable method for the analysis of CYP3A4 activity, and to explore the distributions of the CYP3A4 activity in Chinese children. METHODS: High performance liquid chromatograpy (HPLC) was used to determine the CYP3A4 activity in 85 healthy children and 120 children with acute leukemia. RESULTS: The standard curve had the linear range of 0.01-5 mg/L. The minimal detectable amount was 0.01 mg/L for hydrocortisol and 0.03 mg/L for 6β-hydroxycortisol. Intra- and inter-day assay precisions for hydrocortisol were less than 2% and 5%, respectively, while those for 6β-hydroxycortisol were less than 7% and 10%,respectively. The recovery rate was 98%-106%. The activity range of CYP3A4 in the healthy controls was 2.34 - 48.88,with the average activity of 9.76±6.99. Compared with that of children with acute myelogenous leukemia (AML) (13.97±10.84), there was no statistical difference. The range of CYP3A4 activity in children with acute lymphocytic leukemia (ALL) varied from 2.00 to 585.72, with the average activity of 53.52. It was significantly higher than that of AML (P = 0.0066) and healthy children (P = 0.0065). CONCLUSIONS: This method is rapid and convenient for determining CYP3A4 activity with high sensitivity,accuracy and reproducibility. ALL children have higher CYP3A4 activity than AML and healthy children, while the CYP3A4 activity was similar in the latter two groups.
YUAN Xiao-Jun,GU Long-Jun,ZHAO Hui-Jun et al. Detection of CYP3A4 activity with HPLC in Chinese children with acute leukemia[J]. CJCP, 2005, 7(2): 137-140.
