Efficacy of Paracetamol on Patent Ductus Arteriosus Closure May Be Dose Dependent: Evidence from Human and Murine Studies

Overview

Journal Pediatr Res

Specialties Biology
Pediatrics

Date 2014 Jun 19

PMID 24941212

Citations 25

Authors

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

Affiliations

Soon will be listed here.

Abstract

Background: 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).

Methods: 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.

Results: 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).

Conclusion: 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.

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