Intrathecal Disposition of ARTCEREB Irrigation and Perfusion Solution for Cerebrospinal Surgery in Rats

  • Morioka Yujiro
    Research and Development Center, Otsuka Pharmaceutical Factory, Inc.
  • Nishimura Masuhiro
    Research and Development Center, Otsuka Pharmaceutical Factory, Inc.
  • Takehara Hiroaki
    Research and Development Center, Otsuka Pharmaceutical Factory, Inc.
  • Doi Kazuhisa
    Research and Development Center, Otsuka Pharmaceutical Factory, Inc.
  • Naito Shinsaku
    Research and Development Center, Otsuka Pharmaceutical Factory, Inc.
  • Yamauchi Aiko
    Department of Pharmaceutical Information Science, Graduate School of Pharmaceutical Science, The University of Tokushima

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We investigated the disposition of ARTCEREB® irrigation and perfusion solution (Artcereb) during intrathecal perfusion in a lateral ventricle-cisternal perfusion model in conscious rats. In this perfusion model, the perfusion rate was set at 0.35 ml/kg/h, taking into consideration the clinical perfusion rate (500 ml/60 kg/d). The influence of Artcereb on electrolytes in cerebrospinal fluid (CSF) and blood were then investigated. After 24 h of ventriculocisternal perfusion with Artcereb using the push-pull method, output of K+, Na+ and Cl to the cistern magna was very similar to input of these electrolytes in Artcereb infused intraventricularly. Recovery rates of K+, Na+ and Cl after perfusion were 102%, 105% and 100% when calculated using the recovered perfusion solution. In addition, concentrations of K+, Na+ and Cl in blood remained almost constant at near baseline levels throughout perfusion. Thus, intrathecally perfused Artcereb did not affect electrolyte balance in the CSF and blood. To confirm the dynamics of Artcereb distribution, a whole body autoradiography study was performed at 1 and 6 h after perfusion with 14C-inulin-added Artcereb. Radioactivity was detected in the entire CSF space of the brain, and the cribriform plate in the nasal cavity, and the cerebrospinal cavity. Radioactivity was observed in the bladder, thus suggesting that some 14C-inulin was transferred to the bloodstream via a physiological route, and was excreted renally.

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