Urinary phenylacetylglutamine as dosing biomarker for patients with urea cycle disorders
Urinary phenylacetylglutamine as dosing biomarker for patients with urea cycle disorders
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DOI：
10.1016/j.ymgme.2012.08.006
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发表时间：
2012-11-01
影响因子：
3.8
通讯作者：
Scharschmidt, B. F.
中科院分区：
文献类型：
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作者：
Mokhtarani, M.;Diaz, G. A.;Scharschmidt, B. F.
我们分析了苯丁酸甘油酯（也称为GT 4P或HPN-100）和苯丁酸钠在尿素循环障碍（UCD）患者中可能的给药生物标志物的药代动力学数据。研究设计：这些分析基于来自54名成人和11名儿童UCD患者（6-17岁）的3000多个尿液和血浆数据点，这些患者参加了三项临床研究，比较了苯丁酸甘油酯或苯丁酸钠稳态治疗期间的氨控制和药代动力学。所有患者均接受了苯丁酸当量剂量的甘油苯丁酸酯或苯丁酸钠的交叉方式，并进行了24小时的血液样本和尿液采样的苯丁酸，苯乙酸和苯乙酰glutamin.Results：患者接受了苯丁酸当量剂量的甘油苯丁酸酯的范围从15至31.8克/天和苯丁酸钠的范围从13至31.7克/天。血浆代谢物水平变化很大，苯丁酸、苯乙酸和苯乙酰谷氨酰胺的平均波动指数范围分别为1979%-5690%、843%-3931%和881%-1434%。苯丁酸甘油和苯丁酸钠组儿童患者苯丁酸（以尿苯乙酰谷氨酰胺计）的平均回收率分别为66.4和69.0，成人患者分别为68.7和71.4。尿苯乙酰谷氨酰胺排泄量与剂量的相关性最强（r=0.730，p
We have analyzed pharmacokinetic data for glycerol phenylbutyrate (also GT4P or HPN-100) and sodium phenylbutyrate with respect to possible dosing biomarkers in patients with urea cycle disorders (UCD). Study design: These analyses are based on over 3000 urine and plasma data points from 54 adult and 11 pediatric UCD patients (ages 6-17) who participated in three clinical studies comparing ammonia control and pharmacokinetics during steady state treatment with glycerol phenylbutyrate or sodium phenylbutyrate. All patients received phenylbutyric acid equivalent doses of glycerol phenylbutyrate or sodium phenylbutyrate in a cross over fashion and underwent 24-hour blood samples and urine sampling for phenylbutyric acid, phenylacetic acid and phenylacetylglutamine.Results: Patients received phenylbutyric acid equivalent doses of glycerol phenylbutyrate ranging from 15 to 31.8 g/day and of sodium phenylbutyrate ranging from 13 to 31.7 g/day. Plasma metabolite levels varied widely, with average fluctuation indices ranging from 1979% to 5690% for phenylbutyric acid, 843% to 3931% for phenylacetic acid, and 881% to 1434% for phenylacetylglutamine. Mean percent recovery of phenylbutyric acid as urinary phenylacetylglutamine was 66.4 and 69.0 for pediatric patients and 68.7 and 71.4 for adult patients on glycerol phenylbutyrate and sodium phenylbutyrate, respectively. The correlation with dose was strongest for urinary phenylacetylglutamine excretion, either as morning spot urine (r=0.730, p