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Published on: June 29, 2013
The renal hemodynamic effects of ibuprofen in the newborn rabbit
N S Chamaa1, D Mosig, A Drukker
1Division of Pediatric Nephrology and Department of Pediatrics, University Medical Center, Lausanne, Switzerland.
Insights
Ibuprofen, like indomethacin, can harm newborn kidney function. Studies show ibuprofen significantly reduces urine volume, glomerular filtration rate, and renal blood flow in neonatal rabbits, indicating similar renal side effects.
Area of Science:
- Neonatal pharmacology
- Pediatric nephrology
- Drug safety evaluation
Background:
- Nonsteroidal anti-inflammatory drugs (NSAIDs) are used in neonates for conditions like premature labor and patent ductus arteriosus.
- Indomethacin, a common NSAID, is known to cause renal developmental defects and compromise kidney function in newborns.
- Previous studies indicated potential renal side effects of intravenous indomethacin and aspirin in newborn rabbits.
Purpose of the Study:
- To investigate whether ibuprofen exhibits fewer renal side effects compared to indomethacin in neonatal rabbits.
- To evaluate the dose-dependent effects of ibuprofen on renal function and hemodynamics in a neonatal rabbit model.
Main Methods:
- Neonatal rabbits were administered increasing doses of intravenous ibuprofen (0.02, 0.2, 2.0 mg/kg).
- Key renal parameters including urine volume, urinary sodium excretion, glomerular filtration rate (GFR), and renal plasma flow were measured.
- Renal blood flow, filtration fraction, and renal vascular resistance were calculated.
Main Results:
- Intravenous ibuprofen caused a dose-dependent reduction in urine volume, GFR, and renal blood flow.
- The highest dose of ibuprofen (2 mg/kg) led to a significant fall in filtration fraction and a steep increase in renal vascular resistance.
- Urinary sodium excretion decreased, and significant renal hemodynamic and functional side effects were observed.
Conclusions:
- Acute intravenous administration of ibuprofen results in significant renal side effects in neonatal rabbits.
- The renal adverse effects of ibuprofen were found to be comparable to those previously observed with indomethacin.
- Ibuprofen should be used with caution in neonates due to its potential for compromising renal function.
Abstract:
In early childhood, nonsteroidal anti-inflammatory drugs are mainly used to either prevent or treat premature labor of the mother and patent ductus arteriosus of the newborn infant. The most frequently used prostaglandin-synthesis inhibitor is indomethacin. Fetuses exposed to indomethacin in utero have been born with renal developmental defects, and in both the unborn child and the term and premature newborn this drug may compromise renal glomerular function. The latter has in the past also been observed when i.v. indomethacin or i.v. acetylsalicylic acid (aspirin) were administered to newborn rabbits. The present experiments were designed to evaluate whether ibuprofen has less renal side effects than indomethacin, as claimed. Three groups of anesthetized, ventilated, normoxemic neonatal rabbits were infused with increasing doses of ibuprofen (0.02, 0.2, 2.0 mg/kg body weight) and the following renal parameters were measured: urine volume, urinary sodium excretion, GFR, and renal plasma flow. Renal blood flow, filtration fraction, and the renal vascular resistance were calculated according to standard formulae. Intravenous ibuprofen caused a dose-dependent, significant reduction in urine volume, GFR, and renal blood flow with a fall in filtration fraction in the animals receiving the highest dose of ibuprofen (2 mg/kg body weight). There was a very steep rise in renal vascular resistance. Urinary sodium excretion decreased. These experiments in neonatal rabbits clearly show that acute i.v. doses of ibuprofen also have significant renal hemodynamic and functional side effects, not less than seen previously with indomethacin.
