title: Plasma and cerebrospinal fluid concentrations of indomethacin in children after intravenous administration.
abstract: The objective of this study was to evaluate the cerebrospinal fluid (CSF) permeation of indomethacin in healthy children. The participants (n = 31, aged 4-144 months) received indomethacin (0.35 mg/kg) as a 10-minute intravenous infusion prior to surgery under spinal anaesthesia. A single CSF and plasma sample from each individual was collected 14 to 225 minutes after the infusion. Indomethacin concentrations were determined from the CSF, plasma, and protein-free plasma. Total plasma, protein-free plasma, and CSF concentrations of indomethacin ranged between 90 and 2200 ng/mL (median, 780 ng/mL), 0.3 and 0.8 ng/mL (median, 0.5 ng/mL), and 0.2 and 5.0 ng/mL (median, 1.4 ng/mL), respectively. The CSF to plasma concentration ratio remained less than 0.01. There was no correlation between the administration time and CSF concentrations. Eleven children developed 12 nonserious adverse effects, from which 5 were central nervous system (CNS) effects (agitation). In conclusion, indomethacin permeated into the CSF of children, which enables both desired and adverse CNS effects of indomethacin.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kuopio, PO Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Anne
authors.initials: A
authors.lastname: Mannila
authors.forename: Elina
authors.initials: E
authors.lastname: Kumpulainen
authors.forename: Marko
authors.initials: M
authors.lastname: Lehtonen
authors.forename: Marja
authors.initials: M
authors.lastname: Heikkinen
authors.forename: Merja
authors.initials: M
authors.lastname: Laisalmi
authors.forename: Terhi
authors.initials: T
authors.lastname: Salo
authors.forename: Jarkko
authors.initials: J
authors.lastname: Rautio
authors.forename: Jouko
authors.initials: J
authors.lastname: Savolainen
authors.forename: Hannu
authors.initials: H
authors.lastname: Kokki
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D007223:Infant; D007262:Infusions, Intravenous; D008297:Male; D018709:Statistics, Nonparametric; D013997:Time Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007213:Indomethacin