Departamento de Bioquímica, Instituto de Investigaciones Biomédicas Alberto Sols, Facultad de Medicina de la Universidad Autónoma de Madrid, Madrid, Spain.
J Clin Gastroenterol. 2013 Jul;47(6):501-8. doi: 10.1097/MCG.0b013e318272f507.
Hypolactasia is widespread, yet reliable diagnostic tests are lacking. A new test based on oral administration of 4-galactosylxylose (gaxilose) and urine or serum measurement of D-xylose after cleavage by intestinal lactase is under clinical development. We investigated the optimal dose of gaxilose and calculate cutoff values of D-xylose for that dose.
In the randomized, dose-finding, phase I study, urine and serum pharmacokinetics of D-xylose were determined after oral administration of 6 ascending doses of gaxilose (and placebo) to 12 healthy adult volunteers. In the open, parallel, phase Ib study, 30 volunteers received the doses established for the urine and blood tests and D-xylose was measured. Cutoff values were calculated as 1.96 × SD below the mean value. Safety was assessed through reporting of adverse events.
Gaxilose administration showed a progressive, dose-dependent increase in D-xylose in urine and serum. An optimal gaxilose dose of 0.45 g and urine collection periods of 4 and 5 hours were selected for further studies. For the blood test, a 2.7 g dose was selected and C max measured at 90 minutes. The calculated cutoff values of D-xylose for normal lactase activity were 27.58 and 37.87 mg for the 4- and 5-hour urine tests, respectively, and 0.97 mg/dL for the blood test. There were no treatment-related adverse events.
The methodology described provides a simple, safe test for the evaluation of lactase activity in vivo. Further evaluation of the test as a noninvasive diagnosis of hypolactasia is ongoing in patients with lactose intolerance.
低乳糖酶活性较为普遍，但缺乏可靠的诊断测试。一种新的测试方法正在临床开发中，该方法基于口服 4-半乳糖基木糖（gaxilose），然后通过肠道乳糖酶裂解，测量尿液或血清中的 D-木糖。我们研究了 gaxilose 的最佳剂量，并计算了该剂量下 D-木糖的截断值。
在这项随机、剂量发现、I 期研究中，12 名健康成年志愿者口服递增剂量的 gaxilose（和安慰剂）6 次后，测定尿液和血清中 D-木糖的药代动力学。在开放、平行的 Ib 期研究中，30 名志愿者接受了尿液和血液测试确定的剂量，并测量了 D-木糖。截断值计算为平均值以下 1.96 × SD。通过报告不良事件来评估安全性。
gaxilose 给药后，尿液和血清中 D-木糖呈逐渐、剂量依赖性增加。选择 0.45 g 的最佳 gaxilose 剂量和 4 小时和 5 小时的尿液收集期进行进一步研究。对于血液测试，选择 2.7 g 剂量，C max 在 90 分钟时测量。用于正常乳糖酶活性的 D-木糖截断值分别为 4 小时和 5 小时尿液测试的 27.58 和 37.87 mg，以及血液测试的 0.97 mg/dL。没有与治疗相关的不良事件。
描述的方法提供了一种简单、安全的体内评估乳糖酶活性的测试方法。正在对乳糖不耐受患者进行该测试作为无创性诊断低乳糖酶活性的进一步评估。
