Gasthuys Elke, Vermeulen An, Croubels Siska, Millecam Joske, Schauvliege Stijn, van Bergen Thomas, De Bruyne Pauline, Vande Walle Johan, Devreese Mathias
Department of Pharmacology, Toxicology and Biochemistry, Ghent University, Merelbeke, Belgium.
Department of Bio-analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
Front Pharmacol. 2018 Jan 31;9:41. doi: 10.3389/fphar.2018.00041. eCollection 2018.
Desmopressin is used to treat primary nocturnal enuresis in children. Over the years, various formulations of desmopressin were commercialized of which the sublingual melt tablet is preferred in the pediatric population, despite the lack of full PK studies in this population. A full PK study was performed in growing conventional piglets to evaluate if this juvenile animal model can provide supplementary information to complement the information gap in the pediatric population. A desmopressin sublingual melt tablet (120 μg) was administered to 32 male piglets aged 8 days, 4 weeks, 7 weeks, and 6 months (each group = 8). Population PK (pop-PK) analysis was performed to derive the PK parameters, the between- and within-subject variabilities and the effects of covariates. Desmopressin demonstrated two-compartmental PK, with a dual, sequential absorption process, and linear elimination. Body weight was the only significant covariate on clearance and on apparent volume of distribution of the central compartment. In human pediatric trials, no double peak in the absorption phase was observed in the plasma concentration-time curves, possibly due to the sparse sampling strategy applied in those pediatric studies. Therefore, it is recommended to perform additional studies, based on the sampling protocol applied in the current study.
去氨加压素用于治疗儿童原发性夜间遗尿症。多年来，多种去氨加压素制剂已商业化，其中舌下溶片在儿科人群中更受青睐，尽管该人群缺乏完整的药代动力学（PK）研究。在生长中的普通仔猪中进行了一项完整的PK研究，以评估这种幼年动物模型是否可以提供补充信息，以弥补儿科人群中的信息空白。将一片去氨加压素舌下溶片（120μg）给予32只8日龄、4周龄、7周龄和6月龄的雄性仔猪（每组 = 8只）。进行群体药代动力学（pop-PK）分析以得出PK参数、受试者间和受试者内变异性以及协变量的影响。去氨加压素表现出二室PK，具有双重、顺序吸收过程和线性消除。体重是清除率和中央室表观分布容积的唯一显著协变量。在儿科人体试验中，血浆浓度-时间曲线的吸收相中未观察到双峰，这可能是由于这些儿科研究中采用的稀疏采样策略所致。因此，建议根据本研究中应用的采样方案进行额外的研究。
