Clinical pharmacology of ibuprofen in preterm infants: A meta-analysis of published data

Abstract

OBJECTIVES: Ibuprofen is a non-selective anti-inflammatory cyclooxygenase inhibitor drug of the propionic acid class of non-steroidal agents, available without prescription in the USA. In preterm infants, ibuprofen is used to close the Patent Ductus Arteriosus and it was found to be more effective than indomethacin. This metaanalysis determined whether differences exist in the closure rate of Patent Ductus Arteriosus following the oral vs. intravenous ibuprofen administration to preterm infants; it examines metabolism, pharmacokinetics and adverse renal effects of ibuprofen. METHOD: The bibliographic search was performed using PubMed and EMBASE databases as search engines. In addition, the books ''Neofax: a Manual of Drugs Used in the Neonatal Care'' by Young and Mangum and the ''Neonatal Formulary'' were consulted. RESULTS: Patent Ductus Arteriosus closure was 89% with oral ibuprofen (9 reports) vs. 75% with intravenous ibuprofen (13 reports); p = 0.011. The half-life (t 1/2) of ibuprofen is 43.1 and 26.8 hours in infants on the 3 rd and 5 th day of life, respectively. In adults, the half-life of ibuprofen is 2 hours. The rapid shortening of ibuprofen t 1/2 is due to the rapid increase of cytochromes CYP2C9 and CYP2C8 activities, which metabolize ibuprofen and which surge in the liver during the first weeks of life. Ibuprofen reduces the renal glomerular filtration and the sodium tubular transport rates. CONCLUSION: Oral ibuprofen is more effective than intravenous ibuprofen to close patent ductus arteriosus. Ibuprofen has fewer renal adverse effects than intravenous ibuprofen and has the most favourable risk/benefit ratio.

Association of Placebo, Indomethacin, Ibuprofen, and Acetaminophen With Closure of Hemodynamically Significant Patent Ductus Arteriosus in Preterm Infants

“…Although this finding may appear counterintuitive, available pharmacokinetic data support this observation . Pacifici postulated that a slower absorption rate along with a longer half-life prolong the time of contact with the PDA, leading to higher responsiveness of oral ibuprofen compared with the intravenous formulation.…”

Management of Patent Ductus Arteriosus in Premature Infants in 2020

“…This was also seen in a large network meta-analysis ( 74 ). Pacifici suggested that the slower absorption and prolonged half-life with oral administration offered more time for the drug to interact with the PDA and thus made it more effective ( 89 ). However, a study of ELBW infants found that those infants who received oral ibuprofen for PDA closure had a higher rate of PDA reopening compared to those who received IV ibuprofen ( 90 ).…”