Association between oral sildenafil dosing, predicted exposure, and systemic hypotension in hospitalised infants
Association between oral sildenafil dosing, predicted exposure, and systemic hypotension in hospitalised infants
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DOI：
10.1017/s1047951117001639
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发表时间：
2018-01-01
影响因子：
1
通讯作者：
Gonzalez, Daniel
中科院分区：
文献类型：
--
作者：
Hornik, Christoph P.;Onufrak, Nikolas J.;Gonzalez, Daniel
背景：婴儿西地那非剂量、暴露和全身性低血压之间的关系尚不完全清楚。目的：本研究的目的是描述预测的西地那非暴露与住院婴儿低血压之间的关系。方法：从1997年至2013年348例新生儿重症监护病房的电子病历中提取西地那非的剂量和临床特征信息，并采用群体药代动力学模型预测药物暴露。结果：我们确定了232名婴儿接受西地那非，中位剂量为3.2 mg/kg/天（2.0,6.0）。24 h浓度-时间曲线下的中位稳态面积（AUC(24，SS)）和西地那非的最大浓度（C-max,C-SS,C-SIL）分别为712 ng/ml（401, 1561）和129 ng/ml（69, 293）。全身性低血压发生率为9%。在多变量分析中，剂量和暴露均与全身性低血压无关：西地那非剂量的优势比= 0.96(95%可信区间：0.81,1.14)；AUC（24，SS）为0.87 (0.59,1.28)；C-max、C-SS、C-SIL分别为1.19（0.78,1.82）。结论：我们发现西地那非剂量或暴露与全身性低血压没有关联。继续评估西地那非在婴儿中的安全性是有必要的。
Background: The relationship between sildenafil dosing, exposure, and systemic hypotension in infants is incompletely understood. Objectives: The aim of this study was to characterise the relationship between predicted sildenafil exposure and hypotension in hospitalised infants. Methods: 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. Results: 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 (AUC(24,SS)) and maximum concentration of sildenafil (C-max,C-SS,C-SIL) were 712 ngxhour/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 AUC(24,SS); 1.19 (0.78, 1.82) for C-max,C-SS,C-SIL. Conclusions: We found no association between sildenafil dosing or exposure with systemic hypotension. Continued assessment of sildenafil's safety profile in infants is warranted.