2026-05-30T06:17:50Z https://repub.eur.nl/oai

oai:repub.eur.nl:126477 2023-11-26T18:43:04Z

urn:NBN:nl:ui:15-1765/126477 2023-11-26T18:43:04 mods http://hdl.handle.net/1765/126477 hdl:1765/126477 urn:NBN:nl:ui:15-1765/126477 doi:10.1111/bcp.14298 http://hdl.handle.net/1765/126477 https://repub.eur.nl/pub/126477/Repub_126477_O-A.pdf application/pdf Filesize: 4081706 bytes born digital Department of Pediatrics sht supporting host Department of Pharmacy sht supporting host Engbers, A.G.J. (Aline G.J.) Engbers A.G.J. (Aline G.J.) aut author R.B. Flint (Robert) Flint Robert aut author Völler, S. (Swantje) Völler S. (Swantje) aut author J.C.A. de Klerk (Johan C. A.) de Klerk Johan C. A. aut author I.K.M. Reiss (Irwin) Reiss Irwin aut author P. Andriessen (Peter) Andriessen Peter aut author K.D. Liem (Djien) Liem Djien aut author Degraeuwe, P.L.J. (Pieter L.J.) Degraeuwe P.L.J. (Pieter L.J.) aut author Croubels, S. (Siska) Croubels S. (Siska) aut author Millecam, J. (Joske) Millecam J. (Joske) aut author K.M. Allegaert (Karel) Allegaert Karel aut author S.H.P. Simons (Sinno) Simons Sinno aut author C.A.J. Knibbe (Catherijne) Knibbe Catherijne aut author Aims: Racemic ibuprofen is widely used for the treatment of preterm neonates with patent ductus arteriosus. Currently used bodyweight-based dosing guidelines are based on total ibuprofen, while only the S-enantiomer of ibuprofen is pharmacologically active. We aimed to optimize ibuprofen dosing for preterm neonates of different ages based on an enantiomer-specific population pharmacokinetic model. Methods: We prospectively collected 210 plasma samples of 67 preterm neonates treated with ibuprofen for patent ductus arteriosus (median gestational age [GA] 26 [range 24–30] weeks, median body weight 0.83 [0.45–1.59] kg, median postnatal age [PNA] 3 [1–12] days), and developed a population pharmacokinetic model for S- and R-ibuprofen. Results: We found that S-ibuprofen clearance (CLS, 3.98 mL/h [relative standard error {RSE} 8%]) increases with PNA and GA, with exponents of 2.25 (RSE 6%) and 5.81 (RSE 15%), respectively. Additionally, a 3.11-fold higher CLS was estimated for preterm neonates born small for GA (RSE 34%). Clearance of R-ibuprofen was found to be high compared to CLS (18 mL/h [RSE 24%]), resulting in a low contribution of R-ibuprofen to total ibuprofen exposure. Current body weight was identified as covariate on both volume of distribution of S-ibuprofen and R-ibuprofen. Conclusion: S-ibuprofen clearance shows important maturation, especially with PNA, resulting in an up to 3-fold increase in CLS during a 3-day treatment regimen. This rapid increase in clearance needs to be incorporated in dosing guidelines by adjusting the dose for every day after birth to achieve equal ibuprofen exposure. British Journal of Clinical Pharmacology 13981 03065251 2020-04-06 en English enantiomers ibuprofen patent ductus arteriosus population pharmacokinetics preterm neonates Enantiomer specific pharmacokinetics of ibuprofen in preterm neonates with patent ductus arteriosus text info:eu-repo/semantics/article 307463486 298695111 http://purl.org/eprint/accessRights/OpenAccess