Population Pharmacokinetics of Sildenafil in Term Neonates: Evidence of Rapid Maturation of Metabolic Clearance in the Early Postnatal Period

Mukherjee, Arnab; Dombi, Theresa; Wittke, Bärbel; Lalonde, Richard L.

doi:10.1038/clpt.2008.177

Cited by 97 publications

(111 citation statements)

References 28 publications

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“…Either iNO or endotracheal rhSOD decreased PDE5 activity and restored normal postnatal levels of cGMP (44). These data are concordant with the observation that ROS may compromise GC activity (161) and activate PDE5 expression (45, 106), while rhSOD would prevent such detrimental effects and are also in agreement with clinical studies indicating the usefulness of PDE5-inhibitors, as Sildenafil, in the treatment of PPHN (105,163). A recent study also reported that cyclic stretch is associated with increased OS in pulmonary artery smooth cells along with increased GC expression (151).…”

Section: Newborn Lung Polymorphisms Antioxidant Enzymessupporting

confidence: 78%

The Role of Genetic Polymorphisms in Antioxidant Enzymes and Potential Antioxidant Therapies in Neonatal Lung Disease

Dani

Poggi

2014

Antioxidants & Redox Signaling

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Significance: Oxidative stress is involved in the development of newborn lung diseases, such as bronchopulmonary dysplasia and persistent pulmonary hypertension of the newborn. The activity of antioxidant enzymes (AOEs), which is impaired as a result of prematurity and oxidative injury, may be further affected by specific genetic polymorphisms or an unfavorable combination of more of them. Recent Advances: Genetic polymorphisms of superoxide dismutase and catalase were recently demonstrated to be protective or risk factors for the main complications of prematurity. A lot of research focused on the potential of different antioxidant strategies in the prevention and treatment of lung diseases of the newborn, providing promising results in experimental models. Critical Issues: The effect of different genetic polymorphisms on protein synthesis and activity has been poorly detailed in the newborn, hindering to derive conclusive results from the observed associations with adverse outcomes. Therapeutic strategies that aimed at enhancing the activity of AOEs were poorly studied in clinical settings and partially failed to produce clinical benefits. Future Directions: The clarification of the effects of genetic polymorphisms on the proteomics of the newborn is mandatory, as well as the assessment of a larger number of polymorphisms with a possible correlation with adverse outcome. Moreover, antioxidant treatments should be carefully translated to clinical settings, after further details on optimal doses, administration techniques, and adverse effects are provided. Finally, the study of genetic polymorphisms could help select a specific high-risk population, who may particularly benefit from targeted antioxidant strategies.

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Section: Newborn Lung Polymorphisms Antioxidant Enzymessupporting

confidence: 78%

The Role of Genetic Polymorphisms in Antioxidant Enzymes and Potential Antioxidant Therapies in Neonatal Lung Disease

Dani

Poggi

2014

Antioxidants & Redox Signaling

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“…215 Sildenafil clearance in the early neonatal period is low as a result of the relative immaturity of the hepatic cytochrome P450 system but rapidly increases during the first week of life. 216 Hypotension can occur during the initial loading infusion but was not observed when the loading dose (0.4 mg/kg) was delivered over 3 hours, followed by a maintenance dose of 1.6 mg·kg…”

Section: Pulmonary Vasodilator Therapymentioning

confidence: 99%

Pediatric Pulmonary Hypertension

Abman¹,

Hansmann²,

Archer³

et al. 2015

Circulation

948

405

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Abstract-Pulmonary hypertension is associated with diverse cardiac, pulmonary, and systemic diseases in neonates, infants, and older children and contributes to significant morbidity and mortality. However, current approaches to caring for pediatric patients with pulmonary hypertension have been limited by the lack of consensus guidelines from experts in the field. In a joint effort from the American Heart Association and American Thoracic Society, a panel of experienced clinicians and clinician-scientists was assembled to review the current literature and to make recommendations on the diagnosis, evaluation, and treatment of pediatric pulmonary hypertension. This publication presents the results of extensive literature reviews, discussions, and formal scoring of recommendations for the care of children with pulmonary hypertension. Key Words: AHA Scientific Statements ◼ bronchopulmonary dysplasia ◼ congenital diaphragmatic hernia ◼ congenital heart disease ◼ genetics ◼ persistent pulmonary hypertension of the newborn ◼ sickle cell disease © 2015 by the American Heart Association, Inc., and the American Thoracic Society.Circulation is available at http://circ.ahajournals.org DOI: 10.1161/CIR.0000000000000329 †Deceased. The American Heart Association and the American Thoracic Society make every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.This document was approved by the American Heart Association Science Advisory and Coordinating Committee on May 12, 2015, the American Heart Association Executive Committee on July 22, 2015, and the American Thoracic Society on July 24, 2015.The online-only Data Supplement is available with this article at http://circ.ahajournals.org/lookup/suppl/doi:10.1161/CIR.0000000000000329/-/DC1. The American Heart Association requests that this document be cited as follows: Abman SH, Hansmann G, Archer SL, Ivy DD, Adatia I, Chung WK, Hanna BD, Rosenzweig EB, Raj JU, Cornfield D, Stenmark KR, Steinhorn R, Thébaud B, Fineman JR, Kuehne T, Feinstein JA, Friedberg MK, Earing M, Barst RJ, Keller RL, Kinsella JP, Mullen M, Deterding R, Kulik T, Mallory G, Humpl T, Wessel DL; on behalf of the American Heart Association Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation, Council on Clinical Cardiology, Council on Cardiovascular Disease in the Young, Council on Cardiovascular Radiology and Intervention, Council on Cardiovascular Surgery and Anesthesia, and the American Thoracic Society. Pediatric pulmonary hypertension: guidelines from the American Heart Association and American Thoracic Society. Circulation. 2015;132:2037-2099 Copies: This document is available on the World Wide Web site of the American Heart Associat...

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“…19,25 Oral sildenafil displays an adequate bioavailability (23% in male rats and 38% in humans). 60,61 Sildenafil is metabolized faster in male rats compared with humans, with the elimination half-life of, respectively, 0.4 and 3.7 hours after an oral administration. 61 Dosages in the present study were chosen so that they correspond somewhat to the equivalent recommended amount for human newborns ranging from low doses that are usually initially used to maximal described doses.…”

Section: Discussionmentioning

confidence: 99%

Sildenafil Improves Functional and Structural Outcome of Retinal Injury Following Term Neonatal Hypoxia-Ischemia

Jung

Johnstone

Khoja

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. The purpose of this study was to investigate the effects of sildenafil on retinal injury following neonatal hypoxia-ischemia (HI) at term-equivalent age in rat pups.METHODS. Hypoxia-ischemia was induced in male Long-Evans rat pups at postnatal day 10 (P10) by a left common carotid ligation followed by a 2-hour exposure to 8% oxygen. Shamoperated rats served as the control group. Both groups were administered vehicle or 2, 10, or 50 mg/kg sildenafil, twice daily for 7 consecutive days. Retinal function was assessed by flash electroretinograms (ERGs) at P29, and retinal structure was assessed by retinal histology at P30.RESULTS. Hypoxia-ischemia caused significant functional (i.e., attenuation of the ERG a-wave and b-wave amplitudes and photopic negative response) and structural (i.e., thinning of the total retina, especially the inner retinal layers) retinal damage in the left eyes (i.e., ipsilateral to the carotid ligation). Treatment with the different doses of sildenafil led to a dose-dependent increase in the amplitudes of the ERG a-and b-waves and of the photopic negative response in HI animals, with higher doses associated with greater effect sizes. Similarly, a dose response was observed in terms of improvements in the retinal layer thicknesses.CONCLUSIONS. Hypoxia-ischemia at term-equivalent age induced functional and structural damage mainly to the inner retina. Treatment with sildenafil provided a dose-dependent recovery of retinal function and structure.

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Population Pharmacokinetics of Sildenafil in Term Neonates: Evidence of Rapid Maturation of Metabolic Clearance in the Early Postnatal Period

Cited by 97 publications

References 28 publications

The Role of Genetic Polymorphisms in Antioxidant Enzymes and Potential Antioxidant Therapies in Neonatal Lung Disease

The Role of Genetic Polymorphisms in Antioxidant Enzymes and Potential Antioxidant Therapies in Neonatal Lung Disease

Pediatric Pulmonary Hypertension

Sildenafil Improves Functional and Structural Outcome of Retinal Injury Following Term Neonatal Hypoxia-Ischemia

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