摘要
目的:调查上海地区1169名6~15岁学龄儿童细胞色素P450 3A酶活性(cytochrome P450 3A activity,CA)的分布情况及正常值范围。方法:采用HPLC梯度洗脱法测定尿液中氢化可的松和6p羟基氢化可的松的浓度,以地塞米松为内标,采用HP Hypersil ODS柱(250mm×4mm,5μm),流动相A相为CH3CN,B相为7.56mmol/L(NH4)2SO4溶液,梯度设置;0~6.5min,A:10%,B:90%;6.5~15min,A:35%,B:65%,线性变化;15~24min,A:35%,B:65%;24~28min,A:10%,B:90%,线性变化;28~42min,A:10%,B:90%。柱温30℃;流速1.0ml/min,检测波长240nm。数据分布形态检测采用Kolmogorov-Smirnov检验,男、女儿童酶活性之间的比较采用两个独立样本的t检验。结果:1169名学龄儿童CA分布为左偏态分布,偏度系数为2.66,IgCA呈正态分布,偏度系数为0.027。CA正常值范围为1.00~25.47,男女性之间CA无显著性差异(P=0.919)。将未发育期、发育启动期和发育中期分别设为X=1、2、3,与CA平均值(Y)进行线性回归,得到回归方程为Y=0.685X+3.513(r=0.9999)。结论:确定学龄儿童CA分布情况及其正常值范围,可为制定儿童个体化给药方案和给药剂量提供依据。
Objective: To investigate the distribution of cytochrome P450 3A activity(CA) in the school children aged 6-15 years in Shanghai. Methods: Concentrations of hydrocortisone and 613-hydroxycortisol in urine were determined by gradient HPLC with HP Hypersil ODS column(250 mm×4 mm,5 μm) using dexamethasone as internal standard. The mobile phase A was CH3CN, while mobile phase B was 7.56 mmol/L (NH4)2SO4 water solution. The gradient profile: 0-6.5 min,A: 10% ,B: 90% ;6.5-15 min,A: 35 % ,B:65 % ,linear variation; 15-24 min, A: 35%, B: 65 % ; 24-28 min, A: 10%, B: 90%, linear variation; 28-42 min, A:10 %, B: 90 %. The column temperature was 30 ℃, the flow rate was 1.0 mL/min, and the detection wave length was 240 nm. The frequency distribution of data was examined by the Kolmogorov-Smirnov test. Difference of CA between boys and girls were compared by Student paired t test. Results: The frequency distribution of CA in the 1 169 students was a left skewness distribution with an asymmetry coefficient of 2.66, and IgCA was normally distributed with an asymmetry coefficient of 0. 027. The range of normal values of CA was 1.00-25.47. There was no significant difference of CA between male and female students (P=0. 919). Pubertal development was graded into stage l(before reaching), stage 2(just starting) and stage 3 (intermediate). The linear regression equation between pubertal development (X) and CA(Y) was Y= 0. 685 X + 3.513 ( r = 0. 999 9). Conclusion: It is useful to determine the distribution of CA and the normal value range of CA in Shanghai school-age children for individual dosage regimen.
出处
《药学服务与研究》
CAS
CSCD
2006年第3期176-178,共3页
Pharmaceutical Care and Research