Title:Clinical Pharmacology of Ibuprofen and Indomethacin in Preterm Infants with Patent Ductus Arteriosus
Volume: 10
Issue: 3
Author(s): Gian Maria Pacifici
Affiliation:
Keywords:
ibuprofen, indomethacin, metabolism, neonate, patent-ductus-arteriosus, pharmacodynamics, pharmacokinetics,
renal-side-effects.
Abstract: Background: Ibuprofen and indomethacin are potent non-selective cyclo-oxygenase inhibitors and inhibit prostaglandin
E2 synthesis. The patent ductus arteriosus (PDA) occurs in more than 70% of preterm infants weighing <1500
g. Prostaglandin E2 relaxes smooth muscle, tends to inhibit the closure of PDA, yields vasodilatation of the afferent renal
arterioles and maintains glomerular filtration rate (GFR). Ibuprofen and indomethacin inhibiting prostaglandin E2 synthesis
close PDA and reduce GFR with consequent decrease of urine output and increase of serum creatinine concentrations.
Aims: The aims of this study are to give the definitive estimates of PDA closure rate following ibuprofen or indomethacin
treatment and to evaluate the extent of renal side effects following the administration of these drugs to preterm infants.
Other aims are to review the metabolism and the pharmacokinetics of ibuprofen and indomethacin in preterm infants with
PDA.
Methods: The bibliographic search was performed using PubMed and EMBASE databases as search engines, January
2013 was the cutoff point.
Results: The %PDA closed by ibuprofen (n=24) and indomethacin (n=24) is 77.7±14.1 and 77.3±11.0, respectively. For
ibuprofen, the gestational age of the infants included in the study ranged from 25.0 to 39.0 weeks (mean±SD=29.3±3.1
weeks). The %PDA did not correlate with the gestational age (p=0.2516). For indomethacin, the gestational age of infants
included in the study ranged from 25.0 and 39.0 weeks (mean±SD=29.4±2.9 weeks). The %PDA did not correlate with
the gestational age (p=0.3742). The treatment with ibuprofen reduces the urine output and increases the serum creatinine
concentrations less extensively than indomethacin. The half-life (t1/2) of ibuprofen and indomethacin is lengthened and the
clearance is reduced in preterm infants as compared with fullterm infants.
Conclusions. Ibuprofen and indomethacin are equally effective in closing PDA. Treatment with ibuprofen decreases the
risk of renal failure. Ibuprofen has the most favourable risk/benefit ratio. The rate of metabolism is reduced and t1/2 is
lengthened in prematures as compared with term infants.
