Ibuprofen enantiomers in premature neonates with patent ductus arteriosus: Preliminary data on an unexpected pharmacokinetic profile of S(+)‐ibuprofen. Issue 6 (28th March 2021)

• Record Type: Journal Article
• Authors: Padrini, Roberto; Ancora, Caterina; Nardo, Daniel; De Rosa, Giovanni; Salvadori, Sabrina; Bonadies, Luca; Frigo, Anna Chiara; Lago, Paola
• Is Part Of: Chirality. Volume 33:Issue 6(2021)
• Page Start: 281
• Page End: 291
• Publication Date: 2021-03-28
• Subjects: chiral inversion -- enantiomer -- ibuprofen -- plasma levels -- preterm infants; Chirality -- Periodicals; Pharmaceutical chemistry -- Periodicals; 541.22
• DOI: 10.1002/chir.23308
• Languages: English
• ISSNs: 0899-0042

Abstract

Abstract: S (+)‐ibuprofen ( S ‐IBU) and R (−)‐ibuprofen ( R ‐IBU) concentrations were measured in 16 neonates with patent ductus arteriosus during a cycle of therapy (three intravenous doses of 10–5–5 mg kg −1 at 24‐h intervals), at the end of the first infusion and 6, 24, 48, and 72 h later. Data were analyzed with a PK model that included enantiomer elimination rate constants and the R ‐ to S ‐IBU conversion rate constant. The T ½ of S ‐IBU in the newborn was much longer than in adults (41.8 vs. ≈2 h), whereas the T ½ of R ‐IBU appeared to be the same (2.3 h). The mean fraction of R ‐ to S ‐IBU conversion was much the same as in adults (0.41 vs. ≈0.60). S ‐IBU concentrations measured 6 h after the first dose were higher than at the end of the infusion in 10 out of 16 cases, and in five cases, they remained higher even after 24 h. This behavior is unprecedented and may be attributable to a rapid R ‐to‐ S conversion overlapping with a slow S ‐IBU elimination rate. In 13 of the 16 neonates, S ‐IBU concentrations at 48 and/or 72 h were lower than expected, probably due to the rapid postnatal maturation of the newborn's liver metabolism. Abstract :