Association between oral sildenafil dosing, predicted exposure, and systemic hypotension in hospitalised infants.
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 (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. CONCLUSIONS: We found no association between sildenafil dosing or exposure with systemic hypotension. Continued assessment of sildenafil's safety profile in infants is warranted.
Hornik, CP; Onufrak, NJ; Smith, PB; Cohen-Wolkowiez, M; Laughon, MM; Clark, RH; Gonzalez, D
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