Ibuprofen pharmacokinetics in preterm infants with patent ductus arteriosus

Objective: Our objective was to study the pharmacokinetics of ibuprofen in premature infants with patent ductus arteriosus on day 3 and day 5 after bi rth. Methods: Ibuprofen was administered on days 3, 4, and 5 by a 15-minute intr avenous infusion of 10, 5, and 5 mg/kg, respectively, with the aim of closi ng 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 plasm a 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 +/- standar d deviation). Ibuprofen pharmacokinetics followed a 2-compartment open mode l. Between the first and third doses (day 3 and day 5) there was a signific ant 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 concentrati on-time curve (524 versus 447 mg (.) h/L; P = .01). The decrease in Vd(c) w as most pronounced in patients with a closing ductus. Total body clearance and plasma half-life did not change significantly. No significant differenc es were observed in ibuprofen peak plasma concentrations after the first an d third doses in relation to ductal status after treatment. Conclusion: Ibuprofen pharmacokinetics showed a large interindividual varia tion in premature infants during treatment for patent ductus arteriosus, an d significant changes may occur between day 3 and day 5 after birth in thos e infants with a closing ductus. These findings may have implications for t he treatment schedule with ibuprofen in patients with patent ductus arterio sus.