生长激素替代疗法对生长激素缺乏儿童CYP1A2和黄嘌呤氧化酶活性无影响。

Lack of effect of growth hormone replacement therapy on CYP1A2 and xanthine oxidase activities in growth hormone-deficient children.

作者信息

Mayayo-Sinués Esteban, Fanlo Ana, Sinués Blanca, Mayayo Esteban, Labarta Jose I, García de Jalón Angel, Ferrández-Longás Angel

机构信息

Department of Pharmacology, Medicine School, University of Zaragoza, Domingo Miral s/n, 50009, Zaragoza, Spain.

出版信息

Eur J Clin Pharmacol. 2006 Feb;62(2):123-7. doi: 10.1007/s00228-005-0082-y. Epub 2006 Jan 12.

DOI:10.1007/s00228-005-0082-y

PMID:16408225

Abstract

BACKGROUND AND OBJECTIVES

The recombinant human growth hormone (rhGH) is being increasingly used for a number of metabolic alterations. GH is the main regulator of several hepatic drug metabolizing enzymes in rodents. In addition, GH could play a major role in defining the interface between pharmacogenetics and development. However, little is known about the effect of GH on the activity of hepatic enzymes in children. The aim of this study was to determine the effect of rhGH replacement therapy for 4 weeks on CYP1A2 and xanthine oxidase (XO) activities in children.

METHODS

We used caffeine as a probe drug to assess the enzyme activities at two points in time: before starting GH treatment (day 0) and after 4 weeks on rhGH therapy (day A). A total of 31 GH-deficient children (age range: 4.1-13.1 years, mean age: 9.88+/-2.89 years) participated. Urinary concentrations of caffeine and metabolites were determined by high-performance liquid chromatography (HPLC) to calculate the metabolite ratios: (AFMU+1X+1U)/17U for CYP1A2 and 1U/(1X+1U) for XO.

RESULTS

Four weeks of GH substitution did not importantly alter the markers of the enzyme activities measured in this study. Median values and 95% confidence intervals (CI) at baseline were 5.17 (3.87-5.59) for the CYP1A2 ratio and 0.62 (0.56-0.65) for the XO ratio. These values, after treatment, were 4.57 (3.90-5.97) for the CYP1A2 marker and 0.62 (0.59-0.67) for the XO ratio. Data comparison between periods showed lack of statistically significant differences (P>0.05). The relative changes measured by the ratios of medians and 90% CI were 1.14 (0.90-1.31) and 0.99 (0.94-1.06) for CYP1A2 and XO, respectively.

CONCLUSIONS

The absence of significant changes in the markers of enzyme activities CYP1A2 and XO suggests that rhGH replacement therapy of GH-deficient children for 4 weeks could not noticeably modify the efficacy or toxicity of substrates of these metabolic enzymes.

摘要

背景与目的

重组人生长激素（rhGH）越来越多地用于多种代谢改变。生长激素（GH）是啮齿动物中几种肝脏药物代谢酶的主要调节因子。此外，GH在确定药物遗传学与发育之间的界面方面可能起主要作用。然而，关于GH对儿童肝脏酶活性的影响知之甚少。本研究的目的是确定rhGH替代治疗4周对儿童CYP1A2和黄嘌呤氧化酶（XO）活性的影响。

方法

我们使用咖啡因作为探针药物，在两个时间点评估酶活性：开始GH治疗前（第0天）和rhGH治疗4周后（第A天）。共有31名生长激素缺乏儿童（年龄范围：4.1 - 13.1岁，平均年龄：9.88±2.89岁）参与。通过高效液相色谱法（HPLC）测定尿中咖啡因及其代谢物的浓度，以计算代谢物比率：CYP1A2的（AFMU + 1X + 1U）/17U和XO的1U/（1X + 1U）。

结果

4周的GH替代治疗并未显著改变本研究中测定的酶活性标志物。基线时CYP1A2比率的中位数和95%置信区间（CI）为5.17（3.87 - 5.59），XO比率为0.62（0.56 - 0.65）。治疗后，CYP1A2标志物的值为4.57（3.90 - 5.97），XO比率为0.62（0.59 - 0.67）。各时间段数据比较显示无统计学显著差异（P>0.05）。通过中位数比率和90%CI测量的相对变化，CYP1A2和XO分别为1.14（0.90 - 1.31）和0.99（0.94 - 1.06）。