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An opportunistic study evaluating pharmacokinetics of sildenafil for the treatment of pulmonary hypertension in infants

Journal of Perinatology volume 36, pages 744–747 (2016)Cite this article

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Abstract

Objective:

The objective of this study is to assess sildenafil and N-desmethyl sildenafil (DMS) exposure in infants receiving sildenafil for the treatment of pulmonary hypertension (PH).

Study design:

Data were collected from six infants receiving sildenafil for the treatment of PH and plasma samples were collected at the time of routine laboratory blood draws. The echocardiography results were assessed for improvement in right ventricular (RV) hypertension following sildenafil treatment.

Result:

The median (range) sildenafil and DMS concentrations were 27.4 ng ml−1 (2.6 to 434.0) and 105.5 ng ml−1 (3.6 to 314.0), respectively. The median metabolite-to-parent ratio was higher in infants receiving co-medications that can induce cytochrome P450 (CYP) enzymes (5.2 vs 0.7). The echocardiography results showed improvement in RV hypertension for the majority of infants (5/6).

Conclusion:

The concentrations of sildenafil and DMS were within the previously observed ranges. Our results suggest that caution may be warranted when CYP-related co-medications are administered during sildenafil treatment for PH.

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Acknowledgements

Research reported in this publication was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (5 T32 GM086330-04).

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Authors and Affiliations

  1. Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    N Thakkar, D Gonzalez & N R Zane

  2. Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA

    M Cohen-Wolkowiez

  3. Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA

    M Cohen-Wolkowiez

  4. Department of Pediatrics, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    M M Massaro, J Bernhardt & M M Laughon

Authors
  1. N Thakkar
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  2. D Gonzalez
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  3. M Cohen-Wolkowiez
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  4. M M Massaro
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  5. J Bernhardt
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  6. N R Zane
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  7. M M Laughon
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Corresponding author

Correspondence to M M Laughon.

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Competing interests

DG receives research support through 1K23HD083465-01 from the National Institute of Child Health and Human Development (NICHD) and from the nonprofit organization Thrasher Research Fund (www.thrasherresearch.org). MC-W receives support for research from the National Institutes of Health (NIH) (1R01-HD076676-01A1), the National Center for Advancing Translational Sciences of the NIH (UL1TR001117), the National Institute of Allergy and Infectious Diseases (HHSN272201500006I and HHSN272201300017I), the NICHD (HHSN275201000003I), the Food and Drug Administration (1U01FD004858-01), the Biomedical Advanced Research and Development Authority (HHSO100201300009C), the nonprofit organization Thrasher Research Fund (www.thrasherresearch.org) and from industry (CardioDx and Durata Therapeutics) for drug development in adults and children (www.dcri.duke.edu/research/coi.jsp). MML receives support from the US government for work in neonatal clinical pharmacology (National Heart, Lung and Blood Institute: R34 HL124038: PI, Laughon; Pediatric Trials Network: Government Contract HHSN267200700051C, PI: Benjamin; and NICHD: 1K23HL092225, PI: Laughon), as the satellite site PI for the NICHD Neonatal Research Network (5U10HD040492, PI: Cotten) and from industry for drug development or member of data safety monitoring boards (Abbvie, Astellas Pharma, Pfizer and MediPost). All other authors declare no conflict of interest.

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Thakkar, N., Gonzalez, D., Cohen-Wolkowiez, M. et al. An opportunistic study evaluating pharmacokinetics of sildenafil for the treatment of pulmonary hypertension in infants. J Perinatol 36, 744–747 (2016). https://doi.org/10.1038/jp.2016.79

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