Quantification of Cerebrospinal Fluid Proteins in Children by High-Resolution Agarose Gel Electrophoresis

Barnard, Karin; Herold, Ralf; Siemes, H.; Siegert, Martín J.

doi:10.1177/088307389801300201

Cited by 9 publications

(8 citation statements)

References 17 publications

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“…One likely explanation for this accumulation of drugs into the CSF is that there is protein binding in the CSF, which has indeed been documented for indomethacin 31 . The concentration of proteins in the CSF is approximately 0.5% of that in plasma 32 , 33 . It seems likely that the accumulation of naproxen into the CSF is, to some extent, a result of high lipophilicity and protein binding.…”

Section: Discussionmentioning

confidence: 92%

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Plasma and Cerebrospinal Fluid Pharmacokinetics of Naproxen in Children

Välitalo

Kumpulainen

Manner

et al. 2012

The Journal of Clinical Pharma

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The aim of this study was to characterize pediatric pharmacokinetics and central nervous system exposure of naproxen after oral administration. The pharmacokinetics of naproxen was studied in 53 healthy children aged 3 months to 12 years undergoing surgery with spinal anesthesia. Children received preoperatively a single dose of 10 mg/kg oral naproxen suspension. A single cerebrospinal fluid (CSF) sample (n = 52) was collected at the induction of anesthesia, and plasma samples (n = 270) were collected before, during, and after the operation (up to 51 hours after administration). A population pharmacokinetic model was built using the NONMEM software. Naproxen concentrations in plasma were well described by a 2-compartment model. The estimated oral clearance (CL/F) was 0.62 L/h when linearly scaled by weight to 70 kg. The apparent volume of distribution at steady state (Vss/F) was 12.5 L /70 kg. The findings are consistent with previously reported pharmacokinetic parameters for children older than 5 years. Naproxen permeated into the CSF and reached CSF concentrations that were 4 times higher than unbound plasma concentrations. Based on these data, weight can be used as a basis for naproxen dosing in children older than 3 months of age.

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Section: Discussionmentioning

confidence: 92%

“…31 The concentration of proteins in the CSF is approximately 0.5% of that in plasma. 32,33 It seems likely that the accumulation of naproxen into the CSF is, to some extent, a result of high lipophilicity and protein binding. However, the possibility of active uptake cannot be ruled out.…”

Section: Discussionmentioning

confidence: 99%

Plasma and Cerebrospinal Fluid Pharmacokinetics of Naproxen in Children

Välitalo

Kumpulainen

Manner

et al. 2012

The Journal of Clinical Pharma

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“…One likely explanation for this accumulation of drugs into the CSF is that there is protein binding in the CSF, which has indeed been documented for indomethacin [30]. The concentration of proteins in CSF is about 0.5% of that in plasma [31,32]. It seems likely that the accumulation of flurbiprofen into the CSF is, to some extent, a result of high lipophilicity and protein binding.…”

Section: Figurementioning

confidence: 96%

Plasma and cerebrospinal fluid pharmacokinetics of flurbiprofen in children

Kumpulainen

Välitalo

Kokki

et al. 2010

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECTFlurbiprofen is a commonly used non-steroidal anti-inflammatory drug in children to treat pain and fever. There is limited information on the pharmacokinetics of flurbiprofen in children and no data on the cerebrospinal fluid permeation of flurbiprofen. WHAT THIS STUDY ADDSOur population pharmacokinetic model indicates that weight-based dosing of flurbiprofen is appropriate in children older than 6 months. The bioavailability of oral flurbiprofen syrup is high, 71-91%, and thus, the oral syrup provides accurate dosing in paediatric patients. Cerebrospinal fluid concentrations of flurbiprofen are markedly higher than the unbound plasma concentrations. AIMSThis study was designed to characterize paediatric pharmacokinetics and central nervous system exposure of flurbiprofen. METHODSThe pharmacokinetics of flurbiprofen were studied in 64 healthy children aged 3 months to 13 years, undergoing surgery with spinal anaesthesia. Children were administered preoperatively a single dose of flurbiprofen intravenously as prodrug (n = 27) or by mouth as syrup (n = 37). A single cerebrospinal fluid (CSF) sample (n = 60) was collected at the induction of anaesthesia, and plasma samples (n = 304) before, during and after the operation (up to 20 h after administration). A population pharmacokinetic model was built using the NONMEM software package. RESULTSFlurbiprofen concentrations in plasma were well described by a three compartment model. The apparent bioavailability of oral flurbiprofen syrup was 81%. The estimated clearance (CL) was 0.96 l h -1 70 kg -1 . Age did not affect the clearance after weight had been included as a covariate. The estimated volume of distribution at steady state (Vss) was 8.1 l 70 kg -1. Flurbiprofen permeated into the CSF, reaching concentrations that were seven-fold higher compared with unbound plasma concentrations. CONCLUSIONSFlurbiprofen pharmacokinetics can be described using only weight as a covariate in children above 6 months, while more research is needed in neonates and in younger infants.

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“…Local anesthetics are highly protein bound compounds, and because protein concentration in cerebrospinal fluid is low, most of the intrathecally injected local anesthetic should be protein‐free (53). However, after spinal injection, plasma concentrations are very low, and thus, the risk of systemic toxicity is unlikely.…”

Section: Local Anesthetics Used For Spinal Blocksmentioning

confidence: 99%

Spinal blocks

Kokki

2011

Pediatric Anesthesia

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Every anesthetist should have the expertise to perform lumbar puncture that is the prerequisite to induce spinal anesthesia. Spinal anesthesia is easy and effective technique: small amount of local anesthetic injected in the lumbar cerebrospinal fluid provides highly effective anesthesia, analgesia, and sympathetic and motor block in the lower part of the body. The main limitation of spinal anesthesia is a variable and relatively short duration of the block with a single-injection of local anesthetic. With appropriate use of adjuvant or combining spinal anesthesia with epidural anesthesia, the analgesic action can be controlled in case of early recovery of initial block or in patients with prolonged procedures. Contraindications are rare. Bleeding disorders and any major dysfunction in coagulation system are rare in children, but spinal anesthesia should not be used in children with local infection or increased intracranial pressure. Children with spinal anesthesia may develop the same adverse effects as has been reported in adults, but in contrast to adults, cardiovascular deterioration is uncommon in children even with high blocks. Most children having surgery with spinal anesthesia need sedation, and in these cases, close monitoring of sufficient respiratory function and protective airway reflexes is necessary. Postdural puncture headache and transient neurological symptoms have been reported also in pediatric patients, and thus, guardians should be provided instructions for follow-up and contact information if symptoms appear or persist after discharge. Epidural blood patch is effective treatment for prolonged, severe headache, and nonopioid analgesic is often sufficient for transient neurological symptoms.

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Quantification of Cerebrospinal Fluid Proteins in Children by High-Resolution Agarose Gel Electrophoresis

Cited by 9 publications

References 17 publications

Plasma and Cerebrospinal Fluid Pharmacokinetics of Naproxen in Children

Plasma and Cerebrospinal Fluid Pharmacokinetics of Naproxen in Children

Plasma and cerebrospinal fluid pharmacokinetics of flurbiprofen in children

Spinal blocks

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