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Ibuprofen pharmacokinetics in preterm infants with patent ductus arteriosus
B Van Overmeire1, D Touw, P J Schepens
1Department of Pediatrics, Division of Neonatology, University Hospital Antwerp, Wilrijkstreet 10, B2650 Edegem, Belgium.
Insights
Ibuprofen pharmacokinetics in premature infants with patent ductus arteriosus varied significantly. Changes in volume of distribution occurred by day 5, especially in infants with a closing ductus.
Area of Science:
- Neonatal pharmacology
- Pediatric pharmacokinetics
Background:
- Patent ductus arteriosus (PDA) is common in premature infants.
- Ibuprofen is a common treatment for PDA in neonates.
Purpose of the Study:
- To investigate ibuprofen pharmacokinetics in premature infants with PDA on days 3 and 5.
- To assess changes in ibuprofen levels during treatment.
Main Methods:
- 27 premature infants with PDA received ibuprofen intravenously.
- Ibuprofen doses were 10 mg/kg on day 3 and 5 mg/kg on days 4 and 5.
- Plasma concentrations were measured using HPLC at multiple time points.
Main Results:
- Ibuprofen followed a 2-compartment open model.
- Volume of distribution (Vd(c)) and AUC significantly decreased from day 3 to day 5 (P=.03 and P=.01).
- Decreased Vd(c) was most notable in infants with a closing ductus.
Conclusions:
- Significant interindividual variation in ibuprofen pharmacokinetics was observed.
- Changes in Vd(c) and AUC occur between days 3 and 5 in infants with a closing ductus.
- Findings suggest potential implications for ibuprofen dosing schedules in neonates with PDA.
Objective:
Our objective was to study the pharmacokinetics of ibuprofen in premature infants with patent ductus arteriosus on day 3 and day 5 after birth.
Methods:
Ibuprofen was administered on days 3, 4, and 5 by a 15-minute intravenous infusion of 10, 5, and 5 mg/kg, respectively, with the aim of closing the ductus arteriosus. Blood samples were drawn at time zero and at 0.5, 1, 2, 4, 12, and 24 hours after the first and third doses. Ibuprofen plasma concentrations were assayed by HPLC.
Results:
A total of 27 premature infants were included (gestational age, 28.6 +/- 1.9 weeks; birth weight, 1250 +/- 460 g; values are mean +/- standard deviation). Ibuprofen pharmacokinetics followed a 2-compartment open model. Between the first and third doses (day 3 and day 5) there was a significant decrease of the volume of distribution of the central compartment (Vd(c)) (0.244 versus 0.171 L/kg; P =.03) and area under the plasma concentration-time curve (524 versus 447 mg. h/L; P =.01). The decrease in Vd(c) was most pronounced in patients with a closing ductus. Total body clearance and plasma half-life did not change significantly. No significant differences were observed in ibuprofen peak plasma concentrations after the first and third doses in relation to ductal status after treatment.
Conclusion:
Ibuprofen pharmacokinetics showed a large interindividual variation in premature infants during treatment for patent ductus arteriosus, and significant changes may occur between day 3 and day 5 after birth in those infants with a closing ductus. These findings may have implications for the treatment schedule with ibuprofen in patients with patent ductus arteriosus.