目的 了解厦门地区学龄前儿童细胞色素P450 3A酶(CYP3A)及分布活性特征。方法 用氢化可的松(HC)非侵入性探针法, 利用高效液相色谱(HPLC)测定尿液中6β-羟基氢化可的松(6β-OHC)、氢化可的松(HC)的浓度, 以两者的浓度比定量表示CYP3A酶活性。结果 287名儿童酶活性呈左偏态分布, 中位数为2.61, 四分位数间距为3.97。结论 不同性别间酶活性水平无显著性差别;随着年龄的升高, 酶活性水平呈现降低的趋势(P<0.05), 与年龄具有相关性;3岁组明显高于4岁组(P<0.05)。
Abstract
OBJECTIVE To investigate the CYP3A activity and its characteristics of distribution in the pre-school children in Xiamen. METHODS Using hydrocortisone as a noninvasive probe, urine concentrations of hydrocoritisone ydrocortisone and 6β-hydroxycortisol were determined by HPLC method.The urinary ratio of 6β-hydroxycortisol/ hydrocortisone was used to quantify CYP3A activity. RESULTS The CYP3A activity in the 287 healty children showed a skewed to the left distribution.The median value was 2.61 and the value of quartile range was 3.97. CONCLUSION There is no significant difference in CYP3A activity in gender. With increasing of ages, the CYP3A activity shows the decreasing tendency.The results show a statistic correlation between the ages and CYP3A activity.The value of CYP3A activity in age 3 group is higher than age 4 group.
关键词
CYP3A /
氢化可的松 /
6β-羟基氢化可的松 /
高效液相色谱法 /
学龄前儿童
{{custom_keyword}} /
Key words
CYP3A /
hydrocortisone /
6β-hydroxycortisol /
HPLC /
children at pre-school age
{{custom_keyword}} /
中图分类号:
R969.1
{{custom_clc.code}}
({{custom_clc.text}})
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] HUANG M, WANG H, PING J, et al. Analysis of CYP3A4 gene mutation in han population of China. Chin J Clin Pharm Ther(中国临床药理学与治疗学), 2006, 11(3):300-304. [2] GAO M M, DENG W Y, CHEN S Q, et al. Detection of mutation frequency in human CYP3A4 gene exon 9 . J Mod Clin Med Bioengineer(中华生物医学工程杂志), 2005, 11(5):379-381. [3] YOKOI T. Essentials for starting a pediatric clinical study (1):Pharmacokinetics in children. Toxicol Sci, 2009, 34(2):307-312. [4] Manoranjenni Chetty1, Donald Mattison. Sex differences in the clearance of CYP3A4 substrates:Exploring possible reasons for the substrate dependency and lack of consensus. Curr Drug Metab, 2012, 13:778-786. [5] DAVID J, GREENBLATT, LISA L. Gender has a small but statistically significant effect on clearance of CYP3A substrate drugs. J Clin Pharmacol, 2008, 48:1350-1355. [6] BAKER S D, VAN SCHAIK R H, RIVORY L P, et al. Factors affecting cytochrome P450 3A activity in cancer patients. Clin Cancer Res, 2004, 10(24):8341-8350. [7] TANAKA T, OKUDA T, YAMAMOTO Y. Characterization of the CYP3A4 active site by homology modeling. Chem Pharm Bull, 2004, 52(7):830-835. [8] CHEN M L, ZHANG S G, CAI W M. Pupils of junior school CYP3A activity distribution in hanghai area. Chin J Clin Pharm(中国临床药学杂志), 2007, 16(4):227-230. [9] LU X T, ZHANG S G, ZHANG J, et al. 208 Children CYP 3A activity distribution in hanghai area. Chin J Hosp Pharm(中国医院药学杂志), 2007, 27(3):336-339. YIN O Q, SHI X, TOMLINSON B, et al. Interindividual and intraindividual varia bility of the urinary 6beta-hydroxycortis/cortisol ratio in Chinese subjects:Implications of its use for evaluating CYP3A activity. Clin Pharmacol, 2004, 44(12):1412-1417. LIN Y, ANDERSON G D, KANTOR E, et al. Differences in the urinary excretion of 6-beta-hydroxycortisol/cortisol between Asian and Caucasian womem. Clin Pharmacol, 1999, 39(6):578-582. ZHANG J, TANG Y N, LU X T, et al. Distribution of morning urine 6β-OHFC/FC in 2430 heathy volunteers of primary-junior school children . Chin J Clin Pharm(中国临床药学杂志), 2008, 17:274-277. TANG Y N, ZHANG J, ZHANG Q, et al. Distribution of activity of cytochrome P450 3A in heathy volunteers of primary-junior school children in Han populationin of China. Chin Pharm J (中国药学杂志), 2007, 42(19):1493-1495.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
基金
厦门市科学技术局(3502Z20094018)资助
{{custom_fund}}