糖皮质激素类药物对学龄前儿童CYP3A酶活性的影响

Effects of Corticosteroids on CYP3A Activity in Children at Pre-school Age

目的：研究糖皮质激素类药物对学龄前儿童体内细胞色素P4503A（CYP3A）酶活性的影响。方法：选择厦门地区528例健康学龄前儿童为正常儿童组;68例支气管炎患儿据给药方案的差异分为雾化吸入组（31例）和静脉给药组（37例）,分别予布地奈德1 mg雾化吸入,bid或甲泼尼龙1-2 mg,ivgtt,bid。采用反相高效液相色谱（RP-HPLC）法测定3组受试儿童尿液中6β-羟基氢化可的松和氢化可的松的质量浓度,以两者质量浓度比来表示CYP3A酶活性。考察3组受试儿童CYP3A酶活性的分布特征及差异。结果：正常儿童组、雾化吸入组、静脉给药组受试儿童CYP3A酶活性均呈左偏态分布（P〈0.05,偏度系数〉1）。3组受试儿童CYP3A酶活性分别为4.28（1.90,7.69）、5.80（2.11,11.23）、7.79（1.93,19.44）,差异有统计学意义（P〈0.05）。正常儿童组酶活性中位数低于静脉给药组,差异有统计学意义（P〈0.05）;雾化吸入组酶活性中位数略高于正常儿童组,静脉给药组酶活性中位数略高于雾化吸入组,但差异均无统计学意义（P〉0.05）。结论：使用糖皮质激素类药物可能会影响学龄前儿童CYP3A酶活性,且全身使用糖皮质激素类药物可改变其酶活性。

OBJECTIVE：To study the effects of corticosteroids on CYP3 A activity in children at pre-school age. METHODS：528 healthy children at pre-school age in Xiamen were included in normal children group;68 children diagnosed as bronchitis were divided into aerosol inhalation group（31 cases） and intravenous administration group（37 cases） according to therapy plan,and they were given budesonide 1 mg,aerosol inhalation,bid or methylprednisolone 1-2 mg,ivgtt,bid. RP-HPLC method was established to determinate the concentrations of 6β-hydroxycortisol and hydrocortisone in urine,and the ratio of 6β-hydroxycortisol and hydrocortisone was used to represent CYP3 A activity. Distribution and difference of children CYP3 A activity were investigated in 3groups. RESULTS：The frequency distribution of CYP3 A activity in all the 3 groups was a left skewness distribution（P〈0.05,coefficient of skewness〉1）. CYP3 A activity of 3 groups were 4.28（1.90,7.69）,5.80（2.11,11.23）and 7.79（1.93,19.44）respectively,with statistical significance（P〈0.05）. Median CYP3 A activity of normal children group was lower than that of intravenous administration,with statistical significance（P〈0.05）. Median CYP3 A activity of aerosol inhalation group was higher than normal children group,median CYP3 A activity of intravenous administration group was higher than aerosol inhalation group,with no statistical significance（P〉0.05）. CONCLUSIONS：Corticosteroids may influence CYP3 A activity in children at pre-school age,and corticosteroids used all over body may change CYP3 A activity.