Efficacy of paracetamol on patent ductus arteriosus closure may be dose dependent: evidence from human and murine studies

Afif El-Khuffash; Amish Jain; David Corcoran; Prakesh S Shah; Christopher W Hooper; Naoko Brown; Stanley D Poole; Elaine L Shelton; Ginger L Milne; Jeff Reese; Patrick J McNamara

doi:10.1038/pr.2014.82

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Efficacy of paracetamol on patent ductus arteriosus closure may be dose dependent: evidence from human and murine studies

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Efficacy of paracetamol on patent ductus arteriosus closure may be dose dependent: evidence from human and murine studies

Afif El-Khuffash, Amish Jain, David Corcoran, Prakesh S Shah, Christopher W Hooper, Naoko Brown, Stanley D Poole, Elaine L Shelton, Ginger L Milne, Jeff Reese, …

Pediatric research, Vol.76(3), pp.238-244

09/2014

DOI: 10.1038/pr.2014.82

PMCID: PMC4321957

PMID: 24941212

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Abstract

We evaluated the clinical effectiveness of variable courses of paracetamol on patent ductus arteriosus (PDA) closure and examined its effect on the in vitro term and preterm murine ductus arteriosus (DA). Neonates received one of the following three paracetamol regimens: short course of oral paracetamol (SCOP), long course of oral paracetamol (LCOP), and intravenous paracetamol (IVP) for 2-6 d. Pressure myography was used to examine changes in vasomotor tone of the preterm and term mouse DA in response to paracetamol or indomethacin. Their effect on prostaglandin synthesis by DA explants was measured by mass spectroscopy. Twenty-one preterm infants were included. No changes in PDA hemodynamics were seen in SCOP infants (n = 5). The PDA became less significant and eventually closed in six LCOP infants (n = 7). PDA closure was achieved in eight IVP infants (n = 9). On pressure myograph, paracetamol induced a concentration-dependent constriction of the term mouse DA, up to 30% of baseline (P < 0.01), but required >1 µmol/l. Indomethacin induced greater DA constriction and suppression of prostaglandin synthesis (P < 0.05). The clinical efficacy of paracetamol on PDA closure may depend on the duration of treatment and the mode of administration. Paracetamol is less potent than indomethacin for constriction of the mouse DA in vitro.

Ductus Arteriosus - surgery

Ductus Arteriosus - physiopathology

Ductus Arteriosus, Patent - drug therapy

Humans

Acetaminophen - administration & dosage

Ductus Arteriosus, Patent - metabolism

Dose-Response Relationship, Drug

Ligation

Ductus Arteriosus, Patent - diagnosis

Time Factors

Blood Pressure - drug effects

Ductus Arteriosus, Patent - physiopathology

Prostaglandin Antagonists - administration & dosage

Retrospective Studies

Infant, Newborn

Vasoconstrictor Agents - pharmacology

Ductus Arteriosus, Patent - surgery

Vasoconstrictor Agents - administration & dosage

Drug Administration Schedule

Administration, Oral

Ductus Arteriosus - metabolism

Treatment Outcome

Vasoconstriction - drug effects

Indomethacin - pharmacology

Cyclooxygenase Inhibitors - pharmacology

Administration, Intravenous

Animals

Ductus Arteriosus - drug effects

Details

Title: Subtitle: Efficacy of paracetamol on patent ductus arteriosus closure may be dose dependent: evidence from human and murine studies
Creators: Afif El-Khuffash - Department of Pediatrics, The Rotunda Hospital, Dublin, Ireland
Amish Jain - Department of Pediatrics, Mount Sinai Hospital, Toronto, Ontario, Canada
David Corcoran - Department of Pediatrics, The Rotunda Hospital, Dublin, Ireland
Prakesh S Shah - Department of Pediatrics, Mount Sinai Hospital, Toronto, Ontario, Canada
Christopher W Hooper - Division of Neonatology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee
Naoko Brown - Division of Neonatology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee
Stanley D Poole - Division of Neonatology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee
Elaine L Shelton - Division of Neonatology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee
Ginger L Milne - Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
Jeff Reese - Division of Neonatology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee
Patrick J McNamara - 1] Department of Neonatology, The Hospital for Sick Children, Toronto, Ontario, Canada Department of Physiology and Experimental Medicine, Hospital for Sick Children, Toronto, Ontario, Canada
Resource Type: Journal article
Publication Details: Pediatric research, Vol.76(3), pp.238-244
DOI: 10.1038/pr.2014.82
PMID: 24941212
PMCID: PMC4321957
ISSN: 0031-3998
eISSN: 1530-0447
Grant note: R01 HL109199 / NHLBI NIH HHS R01 HL096967 / NHLBI NIH HHS
Language: English
Date published: 09/2014
Academic Unit: Stead Family Department of Pediatrics; Neonatology; Internal Medicine
Record Identifier: 9984093596002771

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