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Plasma and Cerebrospinal Fluid Concentrations of Indomethacin in Children After Intravenous Administration

From the Department of Pharmaceutical Chemistry (Ms Mannila, Mr Lehtonen, Ms Salo, Dr Rautio, Dr Savolainen) and the Department of Pharmacology and Toxicology (Ms Kumpulainen, Dr Kokki), University of Kuopio, Finland, and the Department of Anaesthesiology and Intensive Care (Ms Kumpulainen, Dr Laisalmi, Dr Kokki) and the Department of Surgery (Dr Heikkinen), Kuopio University Hospital, Finland.

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.

Key Words: Central nervous system • cerebrospinal fluid • children • indomethacin

Address for reprints: Anne Mannila, Department of Pharmaceutical Chemistry, University of Kuopio, PO Box 1627, FI-70211 Kuopio, Finland.

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