NEW YORK (Reuters Health) – Among very low birth weight (VLBW) preterm infants, those treated with oral ibuprofen for patent ductus arteriosus have higher rates of closure than those given ibuprofen intravenously, Turkish researchers report. Moreover, renal side effects with oral treatment seem generally tolerable.

Dr. Omer Erdeve and colleagues with the Zekai Tahir Burak Maternity Teaching Hospital, in Ankara, note in the November 22 online issue of the Journal of Pediatrics that intravenous ibuprofen is not available in most countries and is more expensive than the oral form.

“If oral ibuprofen were as efficient as intravenous ibuprofen with no greater adverse effects,” they point out, “its simple administration and lower cost would be important advantages.”

To investigate this issue, the team performed a prospective, randomized study to compare the efficacy and safety of oral versus intravenous ibuprofen for the pharmacological closure of patent ductus arteriosus in VLBW infants.

As the authors note, “the limited drug-metabolizing enzyme activity of preterm newborn infants increases their susceptibility to renal side effects,” and they used the serum cystatin-C level, “which reflects the glomerular filtration rate (GFR) better than creatinine,” to monitor kidney function.

The 102 VLBW infants in the study received either intravenous or oral ibuprofen at an initial dose of 10 mg/kg, followed by 5 mg/kg at 24 and 48 hours.

“After the first course of the treatment, the PDA closed in 46 (84.6%) of the patients assigned to the oral ibuprofen group versus 31 (62%) of those enrolled in the intravenous ibuprofen group (p=0.011),” according to the report.

“Oral ibuprofen was more effective than intravenous ibuprofen for ductal closure in VLBW infants,” Dr. Erdeve commented via email. “Published data have shown that absorption is slower with oral ibuprofen than with intravenous ibuprofen, and the longer half-life probably prolongs the time of contact with the ductus, leading to a higher response rate.”

However, with a second course of treatment as needed, cumulative closure rates were high in both groups and only one patient in each group required surgical ligation of the patent ductus.

Cystatin-C levels increased significantly in the oral group, but after treatment levels were not significantly between the two groups.

“Our data suggested that oral and intravenous ibuprofen did not have any important renal side effects, as determined using the sensitive marker cys-C,” Dr. Erdeve stated. “Although it was not clinically important, the increase in the cys-C level with the oral form suggests that patients with borderline renal function should be evaluated and followed closely.”

In summarizing, the authors conclude that while oral ibuprofen was more effective for ductal closure with one course of treatment, “the oral form was as safe as the intravenous form in terms of renal tolerance, hyperbilirubinemia, gastrointestinal perforation or bleeding, NEC (necrotizing enterocolitis), intraventricular hemorrhage, CLD (chronic lung disease), and pulmonary hypertension.”

Reference:

Efficacy and Safety of Oral Versus Intravenous Ibuprofen in Very Low Birth Weight Preterm Infants with Patent Ductus Arteriosus

J Pediatr 2010;