De Bruyne Pauline, De Guchtenaere Ann, Van Herzeele Charlotte, Raes Ann, Dehoorne Jo, Hoebeke Piet, Van Laecke Erik, Vande Walle Johan
Department of Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, 3K12D, De Pintelaan 185, 9000, Ghent, Belgium,
Eur J Pediatr. 2014 Feb;173(2):223-8. doi: 10.1007/s00431-013-2108-2. Epub 2013 Aug 30.
Desmopressin 120 μg oral lyophilisate and 200 μg tablet are considered bioequivalent, based on extrapolation of studies in a limited number of adults and on one dose-finding study of desmopressin oral lyophilisate in children. However, no comparative pharmacokinetic study in children was executed confirming this statement. No data are available on the influence of food intake on the bioavailability of desmopressin tablet in a pediatric setting, although studies in adults have documented that food intake results in a significantly lower desmopressin plasma concentration. In this study, we analyzed plasma concentrations of desmopressin oral lyophilisate and tablet with concomitant food intake. Twenty-three children with monosymptomatic nocturnal enuresis (mean age, 12.7 years) were recruited. Two tests were performed on two separate days in identical conditions with a standardized food and fluid intake. Desmopressin was administered as desmopressin tablet or desmopressin oral lyophilisate immediately after a meal. Desmopressin plasma concentration was measured at 1 h, 2 h, and 6 h postdosing. No significant difference in plasma concentration of 120 μg desmopressin oral lyophilisate and 200 μg tablet was demonstrated, even with concomitant food intake. A significant difference in variability was found, identifying a smaller variance for desmopressin oral lyophilisate plasma concentrations at all time points. This study demonstrates comparable plasma levels for desmopressin oral lyophilisate, despite the lower dose. The dosage for desmopressin oral lyophilisate is more predictable due to the significantly smaller variance. Therefore, desmopressin oral lyophilisate seems more suitable, especially in the younger age group for which time interval between dinner and drug administration is limited.
基于对有限数量成年人的研究推断以及一项去氨加压素口服冻干制剂在儿童中的剂量探索研究，120μg口服冻干制剂和200μg片剂的去氨加压素被认为具有生物等效性。然而，尚未进行儿童中的比较药代动力学研究来证实这一说法。尽管成人研究表明食物摄入会导致去氨加压素血浆浓度显著降低，但在儿科环境中，关于食物摄入对去氨加压素片剂生物利用度影响的数据尚无可用。在本研究中，我们分析了同时摄入食物时去氨加压素口服冻干制剂和片剂的血浆浓度。招募了23名单症状性夜间遗尿症儿童（平均年龄12.7岁）。在两个不同的日子里，在相同条件下进行了两项测试，食物和液体摄入量标准化。进食后立即给予去氨加压素片剂或去氨加压素口服冻干制剂。在给药后1小时、2小时和6小时测量去氨加压素血浆浓度。即使同时摄入食物，120μg去氨加压素口服冻干制剂和200μg片剂的血浆浓度也未显示出显著差异。发现变异性存在显著差异，在所有时间点上去氨加压素口服冻干制剂血浆浓度的方差较小。本研究表明，尽管去氨加压素口服冻干制剂剂量较低，但其血浆水平相当。由于方差显著较小，去氨加压素口服冻干制剂的剂量更具可预测性。因此，去氨加压素口服冻干制剂似乎更合适，尤其是在晚餐和给药之间时间间隔有限的较年轻年龄组中。
