Association between oral sildenafil dosing, predicted exposure, and systemic hypotension in hospitalised infants
| Autor: | P. Brian Smith, Daniel Gonzalez, Reese H. Clark, Matthew M. Laughon, Nikolas J. Onufrak, Christoph P. Hornik, Michael Cohen-Wolkowiez |
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| Rok vydání: | 2017 |
| Předmět: |
Male
Sildenafil Hypertension Pulmonary Population Cmax Administration Oral 030204 cardiovascular system & hematology Sildenafil Citrate Article Cohort Studies 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pharmacokinetics 030225 pediatrics Humans Medicine Dosing education education.field_of_study business.industry Infant Newborn Infant General Medicine Odds ratio Phosphodiesterase 5 Inhibitors Confidence interval respiratory tract diseases chemistry Anesthesia Multivariate Analysis Pediatrics Perinatology and Child Health Cohort cardiovascular system Regression Analysis Female Hypotension Cardiology and Cardiovascular Medicine business |
| Zdroj: | Cardiology in the Young. 28:85-92 |
| ISSN: | 1467-1107 1047-9511 |
| DOI: | 10.1017/s1047951117001639 |
| Popis: | BackgroundThe relationship between sildenafil dosing, exposure, and systemic hypotension in infants is incompletely understood.ObjectivesThe aim of this study was to characterise the relationship between predicted sildenafil exposure and hypotension in hospitalised infants.MethodsWe 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.ResultsWe 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.ConclusionsWe found no association between sildenafil dosing or exposure with systemic hypotension. Continued assessment of sildenafil’s safety profile in infants is warranted. |
| Databáze: | OpenAIRE |
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