Association between oral sildenafil dosing, predicted exposure, and systemic hypotension in hospitalised infants
Year: 2017
Type: article
Study design: Observational Study
Abstract: 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.
Source: Cardiology in the Young
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Pfizer, Astellas Pharma, National Institutes of Health, U.S. Food and Drug Administration, Biomedical Advanced Research and Development Authority, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Child Health and Human Development, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1102705159, G1468556634, Use of Physiologically-Based PK/PD Models to Streamline Drug Approvals, G2102029963, Duke CTSA (Composite), Pharmacokinetics, Pharmacodynamics, and Safety of Methylprednisolone in Neonates on Cardiopulmonary Bypass, G2829770695, G3008453, North Carolina Translational & Clinical Sciences Institute (NC TraCS), G4322685311, PATIENT SAFETY RESEARCH DURING NEONATAL CARE (R21), G5139652136, Physiologically-Based Pharmacokinetic Models for Optimal Drug Dosing in Children, Antimicrobial pharmacokinetics and outcomes in vulnerable infants, North Carolina Translational and Clinical Science Institute (NC TraCS), G7177219445, G7378573625, North Carolina Translational & Clinical Sciences Institute (NC TraCS), Echocardiogram to Diagnose Pulmonary Hypertension in Premature Infants
OpenAlex ID: W2742533499