Pharmacokinetics of Cytosine Arabinoside, Methotrexate, Nimustine and Valproic Acid in Cerebrospinal Fluid during Cerebrospinal Fluid Perfusion Chemotherapy
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概要
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This report investigates the pharmacokinetics of cytosine arabinoside (Ara-C), methotrexate (MTX), nimustine (ACNU) and valproic acid (VPA) in cerebrospinal fluid (CSF) during CSF perfusion chemotherapy. A 28-year-old Japanese woman with disseminated glioblastoma was, on admission, on a stable oral regimen of prolonged-release VPA tablets (Depakene^<TM>-R), 400 mg twice a day, for seizure control. Twelve courses of CSF perfusion chemotherapy with Ara-C, MTX, and ACNU were administered. Plasma samples and CSF samples via Ommaya reservoirs were obtained during the eleventh course of treatment. The Ara-C and ACNU concentrations were measured by HPLC. The MTX and VPA concentrations were measured by fluorescence polarization immunoassay.During CSF perfusion chemotherapy, the highest CSF concentrations of Ara-C, MTX, and ACNU were observed at the end of the perfusion and decreased in a monoexponential pattern. The half-lives of Ara-C, MTX, and ACNU were 2.65,3.52,and 0.71 h, respectively. No anticancer drugs were detectable in plasma during CSF perfusion chemotherapy. Before CSF perfusion chemotherapy, the free VPA concentration in plasma was 14.4% of the total VPA concentration. The mean total and free VPA concentrations in plasma were 78.0±0.8 and 10.9±0.3 μg/ml, respectively. The free VPA concentrations in plasma and in CSF were of similar values. At the end of perfusion, the lowest free VPA concentration in CSF was 30.3% of that at the initiation of perfusion. The free VPA concentrations in CSF at 3,7,23,and 47 h after the end of perfusion were 79.8,94.5,100.9,and 100.9% respectively of that at the initiation of perfusion. During CSF perfusion chemotherapy, the ratio of free VPA concentrations to the total VPA in CSF was 86.3±6.9%. The VPA concentrations in CSF rapidly decreased during the CSF perfusion but recovered to pre-treatment levels within 7h.
- 社団法人日本薬学会の論文
- 2000-06-01
著者
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Hori S
Kyoto Pharmaceutical Univ. Kyoto Jpn
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Hori Shigeaki
Department Of Neurosurgery Oita Medical University
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TAKEYAMA MASAHARU
Department of Anesthesiology and Critical Care Medicine, Kagoshima University School of Medicine
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MORIKAWA Norifumi
Department of Clinical Pharmacotherapy, Division of Clinical Pharmacotherapeutics, Graduate School o
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MORI Teruaki
Department of Neurosurgery, Oita Medical University
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ABE Tatsuya
Department of Neurosurgery, Oita Medical University
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KAWASHIMA Hisanori
Department of Clinical Pharmacy, Oita Medical University
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Abe T
Tokyo Univ. Pharmacy & Life Sci. Tokyo Jpn
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Abe Tatsuya
Department Of Neurosurgery Oita University School Of Medicine
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Takeyama Masaharu
Department Of Anesthesiology And Critical Care Medicine Kagoshima University School Of Medicine
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Takeyama M
Oita Univ. Hospital
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Mori Teruaki
Neurosurgery Oita Medical University
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Mori Teruaki
Department Of Neurosurgery Oita Medical University
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Hori Shigeaki
Department Of Neurosurgery Medical College Of Oita
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Kawashima H
Department Of Clinical Pharmacy Oita Medical University
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Kawashima Hisanori
Department Of Clinical Pharmacy Oita Medical University
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Morikawa Norifumi
Department Of Clinical Pharmacotherapy Graduate School Of Biomedical Sciences Hiroshima University
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Morikawa N
Department Of Clinical Pharmacotherapy Hiroshima University
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Abe Tatsuya
Department Of Biochemistry Kyushu University School Of Medicine
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HORI SHIGEAKI
Department of Neurosurgery, Oita Medical University
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Mori Teruaki
Department of Neurology, Nishibeppu National Hospital
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