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

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 (t1/2) of ibuprofen is 43.1 and 26.8 hours in infants on the 3rd and 5th day of life, respectively. In adults, the half-life of ibuprofen is 2 hours. The rapid shortening of ibuprofen t1/2 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.