Department of Pediatric Nephrology, Emma Children's Hospital, Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam, The Netherlands.
Amsterdam Reproduction & Development, Amsterdam, The Netherlands.
Br J Clin Pharmacol. 2024 Jul;90(7):1677-1687. doi: 10.1111/bcp.16066. Epub 2024 Apr 10.
Prednisolone is the cornerstone of treatment for idiopathic nephrotic syndrome in children, but is associated with marked side-effects. Therapeutic drug monitoring using saliva would be a patient-friendly option to monitor prednisolone treatment. To assess the feasibility of saliva monitoring, we described the pharmacokinetics (PK) of unbound prednisolone in plasma and saliva of children with first onset steroid-sensitive nephrotic syndrome (SSNS).
Children (age 2-16 years) with SSNS participating in a randomized, placebo-controlled trial with levamisole were treated with an 18-week tapering schedule of prednisolone. Five serial samples were collected at 4 (saliva) and 8 weeks (saliva and plasma) after first onset. A nonlinear mixed-effects model was used to estimate the PK parameters of unbound prednisolone and the saliva-to-plasma ratio. Monte Carlo simulations were performed to assess the predictive performance of saliva monitoring.
From 39 children, 109 plasma and 275 saliva samples were available. Estimates (relative squared error) of unbound plasma clearance and volume of distribution were 93 (5%) L h 70 kg and 158 (7%) L 70 kg, respectively. Typical saliva-to-plasma ratio was 1.30 (8%). Monte Carlo simulations demonstrated that on basis of 4 saliva samples and a single plasma sample unbound plasma area-under-the-concentration-time curve can be predicted within 20% imprecision in 79% of the patients compared to 87% based on 4 plasma samples.
Saliva proved to be a reliable and patient-friendly option to determine prednisolone plasma exposure in children with SSNS. This opens opportunities for further PK and pharmacodynamics studies of prednisolone in a variety of paediatric conditions.
泼尼松龙是儿童特发性肾病综合征治疗的基石，但与明显的副作用有关。唾液治疗药物监测将是一种方便患者监测泼尼松龙治疗的选择。为了评估唾液监测的可行性，我们描述了初发类固醇敏感性肾病综合征（SSNS）儿童血浆和唾液中未结合的泼尼松龙的药代动力学（PK）。
参加左旋咪唑随机、安慰剂对照试验的 SSNS 儿童接受泼尼松龙 18 周的逐渐减量方案治疗。首次发病后 4 周（唾液）和 8 周（唾液和血浆）采集 5 个连续样本。使用非线性混合效应模型估计未结合的泼尼松龙的 PK 参数和唾液与血浆的比值。进行蒙特卡罗模拟评估唾液监测的预测性能。
从 39 名儿童中，获得了 109 份血浆样本和 275 份唾液样本。未结合的血浆清除率和分布容积的估计值（相对平方误差）分别为 93（5%）L·h·70kg 和 158（7%）L·70kg。典型的唾液与血浆比值为 1.30（8%）。蒙特卡罗模拟表明，基于 4 个唾液样本和 1 个血浆样本，未结合的血浆 AUC 可以在 79%的患者中预测到 20%的不精确性，而基于 4 个血浆样本则可以预测到 87%。
唾液被证明是一种可靠且方便患者的选择，可以确定 SSNS 儿童的泼尼松龙血浆暴露。这为进一步研究各种儿科疾病中泼尼松龙的 PK 和药效动力学提供了机会。
