title: Ibuprofen pharmacokinetics in preterm infants with patent ductus arteriosus.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, Division of Neonatology, University Hospital Antwerp, Wilrijkstreet 10, B2650 Edegem, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: Van Overmeire
authors.forename: D
authors.initials: D
authors.lastname: Touw
authors.forename: P J
authors.initials: PJ
authors.lastname: Schepens
authors.forename: G L
authors.initials: GL
authors.lastname: Kearns
authors.forename: J N
authors.initials: JN
authors.lastname: van den Anker
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004373:Ductus Arteriosus / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D005865:Gestational Age; D006801:Humans; D007052:Ibuprofen / Q000097:blood / Q000493:pharmacokinetics*; D007231:Infant, Newborn; D007234:Infant, Premature; D019102:Infant, Very Low Birth Weight; D007262:Infusions, Intravenous; D015233:Models, Statistical; D012121:Respiration, Artificial; D012127:Respiratory Distress Syndrome, Newborn / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007052:Ibuprofen