Prednisolone Effects on Urine Cross-Linked N-Telopeptides of Type I Collagen (Ntx) Diurnal Rhythms in Children.

IF 4.2 Q3 Pharmacology, Toxicology and Pharmaceutics
Ole D Wolthers, Carsten Heuck
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引用次数: 0

Abstract

Background: Recently, methods for mimicking endogenous cortisol rhythms hereby potentially reducing the risk of systemic adverse effects of exogenous corticosteroids have been patented. Methods for sensitive detection of adverse effects on bone turnover of various doses, administration routes and regimens of exogenous corticosteroids have been patented. Urine cross-linked Ntelopeptides of Type I collagen (Ntx) have been established as a sensitive bone resorption marker and urine levels of Ntx have been found to exhibit a distinct diurnal rhythm.

Objective: To assess whether the timing of administration of prednisolone affects the diurnal rhythm of Ntx in urine.

Methods: Four girls and four boys aged 10.6 to 15.8 (mean 13.2) years with normal weight and height and pubertal stages I-IV were studied in an open randomized 2-periods cross-over trial, with a 1-day run in, and two 4-day periods of 5mg prednisolone in the morning and in the evening, respectively, separated by a 3-week washout period. At run in and on the last day of each treatment period, the first sample of urine was collected from 24.00 to 08.00h in the morning of the day of investigation. Thereafter, urine was collected in 4~hour intervals until 24.00 and in another 08.00h interval from 24.00 to 08.00h.

Results: Compared to run in and morning prednisolone treatment urine Ntx levels were suppressed from 24.00 to 8.00h during treatment with prednisolone in the evening (P < 0.01 for both comparisons) and no statistically significant circadian rhythm was observed. During morning prednisolone treatment Ntx trough and peak levels occurred from 16.00 to 20.00 and 24.00 to 08.00h, respectively, and the Ntx levels were significantly reduced from 12.00 to 20.00h as compared to run in (P < 0.005) and prednisolone treatment in the evening (P < 0.01).

Conclusions: Depending on the time of administration, prednisolone interferes with diurnal rhythms in urine Ntx.

强的松龙对儿童尿I型胶原交联n端肽(Ntx)昼夜节律的影响。
背景:最近,模仿内源性皮质醇节律从而潜在地降低外源性皮质类固醇系统性不良反应风险的方法已获得专利。外源性皮质类固醇的各种剂量、给药途径和方案对骨转换不利影响的敏感检测方法已获得专利。尿交联I型胶原蛋白末端肽(Ntx)已被确定为一种敏感的骨吸收标志物,并且发现尿中Ntx的水平表现出明显的昼夜节律。目的:评价强的松龙给药时间是否影响尿中氨氮的昼夜节律。方法:4名女孩和4名男孩,年龄10.6 ~ 15.8岁(平均13.2岁),体重、身高正常,青春期期为I-IV期,采用开放随机2期交叉试验,1天入组,2天分别在早上和晚上使用5mg强的松龙,中间间隔3周洗脱期。在每个治疗期的磨合和最后一天,于调查当天上午24.00 - 08.00采集第一次尿液样本。此后,每隔4~h采集一次尿液,至24.00,每隔08.00,从24.00至08.00采集一次尿液。结果:与晨跑和早晨泼尼松龙治疗组相比,晚间泼尼松龙治疗组24.00 ~ 8.00h尿Ntx水平均被抑制(P < 0.01),且昼夜节律无统计学意义。上午强的松龙治疗时,Ntx的低谷和高峰分别出现在16.00 ~ 20.00和24.00 ~ 08.00h, 12.00 ~ 20.00h的Ntx水平较晨起(P < 0.005)和晚上强的松龙治疗时显著降低(P < 0.01)。结论:根据给药时间的不同,强的松龙会干扰尿Ntx的昼夜节律。
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来源期刊
CiteScore
3.90
自引率
0.00%
发文量
0
期刊介绍: Recent Patents on Inflammation & Allergy Drug Discovery publishes review articles by experts on recent patents in the field of inflammation and allergy drug discovery e.g. on novel bioactive compounds, analogs and targets. A selection of important and recent patents in the field is also included in the journal. The journal is essential reading for all researchers involved in inflammation and allergy drug design and discovery.
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