Vande Walle Johan G J, Bogaert Guy A, Mattsson Sven, Schurmans Thierry, Hoebeke Piet, Deboe Veerle, Norgaard Jens Peter
Department of Paediatric Nephrology, University of Gent, De Pintelaan 185, 9000 Gent, Belgium.
BJU Int. 2006 Mar;97(3):603-9. doi: 10.1111/j.1464-410X.2006.05999.x.
To determine the pharmacodynamic properties of a new oral lyophilisate formulation of desmopressin (in single doses of 30, 60, 120, 240, 360 or 480 microg) in children with known primary nocturnal enuresis (PNE) and thus identify those dosages that could provide a duration of action corresponding to a typical length of night-time sleep in children with PNE; additional objectives were to determine the safety and tolerability of desmopressin in this population.
Children with PNE (mean three or more wet nights/week), aged 6-12 years, were randomized into a double-blind, placebo-controlled study. An overhydration technique was used before dosing to suppress endogenous vasopressin production and thereby ensure that any antidiuresis could be attributed to treatment. Dosing with desmopressin or placebo occurred when urinary production was >0.13 mL/min/kg. Urinary volume, osmolality and duration of urinary-concentrating action (above three threshold levels: 125, 200 and 400 mOsm/kg) were determined as endpoints.
All 72 participants receiving desmopressin had a pharmacodynamic response to the drug, while there was no change in urinary output in the 12 placebo-treated patients. There was a clear relationship between desmopressin dose and duration of action and osmolality during action, although the three highest-dose groups had similar results. The mean duration of action of desmopressin at the lowest osmolality threshold level was 3.6-10.6 h, according to dose; for the highest threshold, the values were 1.3-8.6 h.
Desmopressin, as the oral lyophilisate, causes a marked decrease in urinary output in hydrated children with PNE. A small dose range (120-240 microg) is likely to control diuresis for a period corresponding to a night's sleep (7-11 h) in most children with PNE. However, some patients might require a higher dose to obtain antidiuresis for the complete night.
确定去氨加压素新型口服冻干制剂（单剂量30、60、120、240、360或480微克）在已知原发性夜间遗尿（PNE）儿童中的药效学特性，从而确定那些作用持续时间能与PNE儿童典型夜间睡眠时间相对应的剂量；其他目的是确定去氨加压素在该人群中的安全性和耐受性。
年龄6至12岁、患有PNE（平均每周尿床3个或更多晚上）的儿童被随机纳入一项双盲、安慰剂对照研究。给药前采用水合过度技术抑制内源性血管加压素的产生，从而确保任何抗利尿作用都可归因于治疗。当尿量产生>0.13毫升/分钟/千克时给予去氨加压素或安慰剂。测定尿量、渗透压以及尿浓缩作用持续时间（高于三个阈值水平：125、200和400毫渗摩尔/千克）作为终点指标。
所有72名接受去氨加压素治疗的参与者对该药物均有药效学反应，而12名接受安慰剂治疗的患者尿量无变化。去氨加压素剂量与作用持续时间以及作用期间的渗透压之间存在明显关系，尽管三个最高剂量组结果相似。根据剂量，去氨加压素在最低渗透压阈值水平下的平均作用持续时间为3.6至10.6小时；对于最高阈值，该值为1.3至8.6小时。
作为口服冻干制剂的去氨加压素可使患有PNE的水合儿童尿量显著减少。小剂量范围（120至240微克）可能在大多数PNE儿童中控制利尿一段时间，相当于一夜睡眠（7至11小时）。然而，一些患者可能需要更高剂量才能在整个夜间获得抗利尿作用。
