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Post-publication Peer Reviews to:
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![[Read P3R]](/icons/misc/sectionDOWN.gif){kind=icon}
additional data on cerebrospinal fluid kinetics of paracetamol in neonates
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karel allegaert, neonatologist University Hospital Gasthuisberg, Leuven, Belgium
Send letter to journal:
karel.allegaert{at}uz.kuleuven.ac.be karel allegaert
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Dear editor, The documentation of cerebrospinal fluid (CSF) penetration and kinetics of intravenous paracetamol (acetaminophen) is of relevance since Anderson et al. illustrated that pharmacokinetics (PK) of CSF approximate closer to the analgesic effect compartment than plasma after enteral administration of paracetamol in children. Peak plasma concentrations were reached 90 to 120 minutes after enteral administration in children with an additional delay of one hour between peak plasma concentration and maximal analgesia (1). We therefore congratulate Kumpalainen et al. on their population pharmacokinetic approach to document plasma-CSF kinetics in children following single intravenous administration of paracetamol (15 mg/kg) and hereby documented an additional time needed (about 1 hour) before maximum CSF concentration was reached 2. We only would like to mention that in addition to observations in adults and the current observations in children, we reported similar observations in two neonates (2,3,4,5). In a first neonate, CSF paracetamol kinetics were documented following single dose administration (4). In a second case, paracetamol CSF kinetics during repeated dose administration were documented (5). We hereby documented a similar delay in peak concentrations between the blood and the CSF compartment. This suggests that there is no overt age- dependent maturation in the permeability of the blood-brain barrier for this drug. In addition, we would like to drawn the attention of the reader to the absence of any significant correlation between plasma and CSF paracetamol concentration during intravenous administration (r = 0.01, 95 % CI r = -0.51 to 0.5) of plasma versus cerebrospinal fluid concentration of paracetamol. It is therefore to be expected that any attempt to document a correlation between plasma paracetamol concentration and a level of analgesia will always remain weak, since plasma concentrations only in part reflects CSF concentration of paracetamol. This phenomenon will be most prominent for the intravenous route compared to enteral administration. References 1.Anderson BJ, Holford NHG, Woollard GA, Chan PLS. Paracetamol plasma and cerebrospinal fluid pharmacokinetics in children. Br J Clin Pharmacol 1998;46:237-243. 2.Kumpalainen E, Kokki H, Halonen T, Heikkinen M, Savolainen J, Laisalmi M. Paracetamol (acetaminophen) penetrates readily into the cerebrospinal fluid of children after intravenous administration. Pediatrics 23007;119:766-71 3.Bannwarth B, Netter P, Lapicque F, Gillet P, Pere P, Boccard E, et al. Plasma and cerebrospinal fluid concentrations of paracetamol after single intravenous dose of propacetamol. Br J Clin Pharmacol 1992;34:79- 81. 4.Allegaert K, Verbesselt R, Devlieger H, de Hoon J, Tibboel D. Cerebrospinal fluid pharmacokinetics of intravenous propacetamol in a former preterm infant. Br J Clin Pharmacol 2004;57:224-5 5.Allegaert K, Devlieger H. Relevance of the blood-brain barrier on compartmental pharmacokinetics of paracetamol. J Paediatr Neurol 2005;3:273-275 Conflict of Interest:None declared |
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