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Association between oral sildenafil dosing, predicted exposure, and systemic hypotension in hospitalised infants

Published online by Cambridge University Press:  08 August 2017

Christoph P. Hornik ,
Nikolas J. Onufrak ,
P. Brian Smith ,
Michael Cohen-Wolkowiez ,
Matthew M. Laughon ,
Reese H. Clark  and
Daniel Gonzalez
Christoph P. Hornik*
Affiliation:
Department of Pediatrics, Duke Clinical Research Institute, Duke University, Durham, North Carolina, United States of America
Nikolas J. Onufrak
Affiliation:
Eshelman 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
P. Brian Smith
Affiliation:
Department of Pediatrics, Duke Clinical Research Institute, Duke University, Durham, North Carolina, United States of America
Michael Cohen-Wolkowiez
Affiliation:
Department of Pediatrics, Duke Clinical Research Institute, Duke University, Durham, North Carolina, United States of America
Matthew M. Laughon
Affiliation:
Department of Pediatrics, Division of Neonatology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
Reese H. Clark
Affiliation:
Pediatrix-Obstetrix Center for Research and Education, Sunrise, Florida, United States of America
Daniel Gonzalez
Affiliation:
Eshelman 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
*
Correspondence to: C. P. Hornik, MD, MPH, Duke Clinical Research Institute, Box 17969, Durham, NC 27715, United States of America. Tel: 919 668 8935; Fax: 919 668 7058; E-mail: [email protected]
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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.

Keywords

Dosingexposuresystemic hypotensioninfantsildenafil
Type
Original Articles
Information
Cardiology in the Young , Volume 28 , Issue 1 , January 2018 , pp. 85 - 92
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Copyright
© Cambridge University Press 2017 

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