Hornik Christoph P, Onufrak Nikolas J, Smith P Brian, Cohen-Wolkowiez Michael, Laughon Matthew M, Clark Reese H, Gonzalez Daniel
1Department of Pediatrics,Duke Clinical Research Institute,Duke University,Durham,North Carolina,United States of America.
2Eshelman School of Pharmacy,Division of Pharmacotherapy and Experimental Therapeutics,The University of North Carolina at Chapel Hill,Chapel Hill,North Carolina,United States of America.
Cardiol Young. 2018 Jan;28(1):85-92. doi: 10.1017/S1047951117001639. Epub 2017 Aug 8.
The relationship between sildenafil dosing, exposure, and systemic hypotension in infants is incompletely understood.
The aim of this study was to characterise the relationship between predicted sildenafil exposure and hypotension in hospitalised infants.
We extracted information on sildenafil dosing and clinical characteristics from electronic health records of 348 neonatal ICUs from 1997 to 2013, and we predicted drug exposure using a population pharmacokinetic model.
We identified 232 infants receiving sildenafil at a median dose of 3.2 mg/kg/day (2.0, 6.0). The median steady-state area under the concentration-time curve over 24 hours (AUC24,SS) and maximum concentration of sildenafil (Cmax,SS,SIL) were 712 ng×hour/ml (401, 1561) and 129 ng/ml (69, 293), respectively. Systemic hypotension occurred in 9% of the cohort. In multivariable analysis, neither dosing nor exposure were associated with systemic hypotension: odds ratio=0.96 (95% confidence interval: 0.81, 1.14) for sildenafil dose; 0.87 (0.59, 1.28) for AUC24,SS; 1.19 (0.78, 1.82) for Cmax,SS,SIL.
We found no association between sildenafil dosing or exposure with systemic hypotension. Continued assessment of sildenafil's safety profile in infants is warranted.
西地那非的给药剂量、暴露量与婴儿系统性低血压之间的关系尚未完全明确。
本研究旨在描述住院婴儿预计的西地那非暴露量与低血压之间的关系。
我们从1997年至2013年348个新生儿重症监护病房的电子健康记录中提取了西地那非给药剂量和临床特征信息，并使用群体药代动力学模型预测药物暴露量。
我们确定了232名接受西地那非治疗的婴儿，中位剂量为3.2毫克/千克/天（2.0，6.0）。24小时浓度-时间曲线下的中位稳态面积（AUC24,SS）和西地那非的最大浓度（Cmax,SS,SIL）分别为712纳克·小时/毫升（401，1561）和129纳克/毫升（69，293）。9%的队列中出现了系统性低血压。在多变量分析中，给药剂量和暴露量均与系统性低血压无关：西地那非剂量的比值比=0.96（95%置信区间：0.81，1.14）；AUC24,SS的比值比为0.87（0.59，1.28）；Cmax,SS,SIL的比值比为1.19（0.78，1.82）。
我们发现西地那非给药剂量或暴露量与系统性低血压之间无关联。有必要继续评估西地那非在婴儿中的安全性。
