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Am J Perinatol 2015; 32(12): 1158-1163
DOI: 10.1055/s-0035-1551671
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Effect of Oral High-dose Ibuprofen on Patent Ductus Arteriosus Closure in Preterm Infants

Shahnaz Pourarian
1   Neonatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
,
Faranak Takmil
2   Department of Pediatrics, Shiraz University of Medical Sciences, Shiraz, Iran
,
Sirous Cheriki
3   Neonatology and Cardiac Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
,
Hamid Amoozgar
3   Neonatology and Cardiac Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
› Author Affiliations
Further Information

Publication History

20 August 2014

13 March 2015

Publication Date:
22 May 2015 (online)

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Abstract

Objective The aim of this study is to compare the efficacy and possible adverse effects of the oral high-dose ibuprofen regimen to that of standard regimen in closing patent ductus arteriosus (PDA).

Study Design This clinical trial study was performed from April 2012 to May 2013 on preterm infants with gestational age < 37 weeks and postnatal age 3 to 7 days with echocardiographic diagnosis of hemodynamically significant PDA. These neonates were randomly assigned to two treatment groups that respectively received high dose (20–10–10 mg/kg/d) and standard dose (10–5–5 mg/kg/d) oral ibuprofen regimen for 3 days. Effect of ibuprofen therapy was evaluated by echocardiography and neonates were followed for renal dysfunction, gastrointestinal complication, bleeding, and hyperbilirubinemia.

Results From a total of 60 enrolled infants, 30 cases received the high dose of ibuprofen and the remaining 30 received the standard dose. Complete ductal closure was observed in 20 (70%) infants treated with high-dose regimen in comparison with 11 (36.7%) in the standard-dose regimen group (p = 0.010). No gastrointestinal, renal, or hematological adverse effects were reported.

Conclusion The high-dose oral ibuprofen seems to be more effective than the current standard dose regimen for PDA closure in premature neonates without increasing the adverse effects.

Keywords

Premature PDA High-Dose Ibuprofen
 

  • References

  • 1 Koch J, Hensley G, Roy L, Brown S, Ramaciotti C, Rosenfeld CR. Prevalence of spontaneous closure of the ductus arteriosus in neonates at a birth weight of 1000 grams or less. Pediatrics 2006; 117 (4) 1113-1121
    CrossrefPubMedSearch in Google Scholar
  • 2 Ellison RC, Peckham GJ, Lang P , et al. Evaluation of the preterm infant for patent ductus arteriosus. Pediatrics 1983; 71 (3) 364-372
    PubMedSearch in Google Scholar
  • 3 Rojas MA, Gonzalez A, Bancalari E, Claure N, Poole C, Silva-Neto G. Changing trends in the epidemiology and pathogenesis of neonatal chronic lung disease. J Pediatr 1995; 126 (4) 605-610
    CrossrefPubMedSearch in Google Scholar
  • 4 Jones RW, Pickering D. Persistent ductus arteriosus complicating the respiratory distress syndrome. Arch Dis Child 1977; 52 (4) 274-281
    CrossrefPubMedSearch in Google Scholar
  • 5 Supapannachart S, Limrungsikul A, Khowsathit P. Oral ibuprofen and indomethacin for treatment of patent ductus arteriosus in premature infants: a randomized trial at Ramathibodi Hospital. J Med Assoc Thai 2002; 85 (4) (Suppl. 04) S1252-S1258
    PubMedSearch in Google Scholar
  • 6 Pourarian Sh, Pishva N, Madani A, Rastegari M. Comparison of oral ibuprofen and indomethacin on closure of patent ductus arteriosus in preterm infants. East Mediterr Health J 2008; 14 (2) 360-365
    PubMedSearch in Google Scholar
  • 7 Lee CH, Chen HN, Tsao LY, Hsiao CC, Lee ML. Oral ibuprofen versus intravenous indomethacin for closure of patent ductus arteriosus in very low birth weight infants. Pediatr Neonatol 2012; 53 (6) 346-353
    CrossrefPubMedSearch in Google Scholar
  • 8 Yadav S, Agarwal S, Maria A , et al. Comparison of oral ibuprofen with oral indomethacin for PDA closure in Indian preterm neonates: a randomized controlled trial. Pediatr Cardiol 2014; 35 (5) 824-830
    CrossrefPubMedSearch in Google Scholar
  • 9 Dani C, Vangi V, Bertini G , et al. High-dose ibuprofen for patent ductus arteriosus in extremely preterm infants: a randomized controlled study. Clin Pharmacol Ther 2012; 91 (4) 590-596
    CrossrefPubMedSearch in Google Scholar
  • 10 Desfrere L, Zohar S, Morville P , et al. Dose-finding study of ibuprofen in patent ductus arteriosus using the continual reassessment method. J Clin Pharm Ther 2005; 30 (2) 121-132
    CrossrefPubMedSearch in Google Scholar
  • 11 Hirt D, Van Overmeire B, Treluyer J-M , et al. An optimized ibuprofen dosing scheme for preterm neonates with patent ductus arteriosus, based on a population pharmacokinetic and pharmacodynamic study. Br J Clin Pharmacol 2008; 65 (5) 629-636
    CrossrefPubMedSearch in Google Scholar
  • 12 Gregory KE, Deforge CE, Natale KM, Phillips M, Van Marter LJ. Necrotizing enterocolitis in the premature infant: neonatal nursing assessment, disease pathogenesis, and clinical presentation. Adv Neonatal Care 2011; 11 (3) 155-164 , quiz 165–166
    CrossrefPubMedSearch in Google Scholar
  • 13 Sasi A, Deorari A. Patent ductus arteriosus in preterm infants. Indian Pediatr 2011; 48 (4) 301-308
    CrossrefPubMedSearch in Google Scholar
  • 14 Yang EM, Song ES, Choi YY. Comparison of oral Ibuprofen and intravenous indomethacin for the treatment of patent ductus arteriosus in extremely low birth weight infants. J Pediatr (Rio J) 2013; 89 (1) 33-39
    CrossrefPubMedSearch in Google Scholar
  • 15 Patel J, Roberts I, Azzopardi D, Hamilton P, Edwards AD. Randomized double-blind controlled trial comparing the effects of ibuprofen with indomethacin on cerebral hemodynamics in preterm infants with patent ductus arteriosus. Pediatr Res 2000; 47 (1) 36-42
    CrossrefPubMedSearch in Google Scholar
  • 16 Van Overmeire B, Smets K, Lecoutere D , et al. A comparison of ibuprofen and indomethacin for closure of patent ductus arteriosus. N Engl J Med 2000; 343 (10) 674-681
    CrossrefPubMedSearch in Google Scholar
  • 17 Guzoglu N, Sari FN, Ozdemir R , et al. Renal and mesenteric tissue oxygenation in preterm infants treated with oral ibuprofen. J Matern Fetal Neonatal Med 2014; 27 (2) 197-203
    CrossrefPubMedSearch in Google Scholar
  • 18 Neumann R, Schulzke SM, Bührer C. Oral ibuprofen versus intravenous ibuprofen or intravenous indomethacin for the treatment of patent ductus arteriosus in preterm infants: a systematic review and meta-analysis. Neonatology 2012; 102 (1) 9-15
    Search in Google Scholar
  • 19 Erdeve O, Yurttutan S, Altug N , et al. Oral versus intravenous ibuprofen for patent ductus arteriosus closure: a randomised controlled trial in extremely low birthweight infants. Arch Dis Child Fetal Neonatal Ed 2012; 97 (4) F279-F283
    CrossrefPubMedSearch in Google Scholar
  • 20 Aranda JV, Varvarigou A, Beharry K , et al. Pharmacokinetics and protein binding of intravenous ibuprofen in the premature newborn infant. Acta Paediatr 1997; 86 (3) 289-293
    CrossrefPubMedSearch in Google Scholar
  • 21 Van Overmeire B, Touw D, Schepens PJ, Kearns GL, van den Anker JN. Ibuprofen pharmacokinetics in preterm infants with patent ductus arteriosus. Clin Pharmacol Ther 2001; 70 (4) 336-343
    CrossrefPubMedSearch in Google Scholar
  • 22 Richards J, Johnson A, Fox G, Campbell M. A second course of ibuprofen is effective in the closure of a clinically significant PDA in ELBW infants. Pediatrics 2009; 124 (2) e287-e293
    CrossrefPubMedSearch in Google Scholar
  • 23 Pezzati M, Vangi V, Biagiotti R, Bertini G, Cianciulli D, Rubaltelli FF. Effects of indomethacin and ibuprofen on mesenteric and renal blood flow in preterm infants with patent ductus arteriosus. J Pediatr 1999; 135 (6) 733-738
    CrossrefPubMedSearch in Google Scholar
  • 24 Soldin OP, Chung SH, Mattison DR. Sex differences in drug disposition. J Biomed Biotechnol 2011; 2011: 187103
    PubMedSearch in Google Scholar
  • 25 Whitley H, Lindsey W. Sex-based differences in drug activity. Am Fam Physician 2009; 80 (11) 1254-1258
    PubMedSearch in Google Scholar