Pharmacokinetics of Etoposide and Carboplatin in Cerebrospinal Fluid and Plasma during Hyperosmotic Disruption of the Blood Brain Barrier and Intraarterial Combination Chemotherapy
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概要
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The present paper investigates the pharmacokinetics of etoposide (VP-16) and carboplatin (CBDCA) in plasma and the cerebrospinal fluid (CSF), in the space left by tumor removal, of patients with glioma. Eight Japanese patients with glioma received a course of hyperosmotic disruption of the blood-brain barrier(HODBBB) and intraarterial combination chemotherapy with 60 mg/m^2 of VP-16 and 300 mg/m^2 of CBDCA. Allpatients were initially administered mannitol, followed by infusion of the anticancer drugs into the right internal carotid artery. Blood samples and samples of CSF in the space left by tumor removal were obtained. VP-16 and CBDCA concentration were measured by HPLC, and the pharmacokinetic parameters of these drugs estimated in CSF and plasma.The plasma concentrations of VP-16 and CBDCA peaked at the end of infusion, then decreased in a bi-exponential decay pattern during the remainder of the treatment period. Both VP-16 and CBDCA were detectable in CSF beginning 0.5h after the initiation of each infusion, and were then slowly eliminated from the space left by tumor removal. The mean maximum CSF concentration of VP-16 and CBDCA was 0.17 and 15.25% of that in plasma, respectively. The mean area under the time-CSF concentration curve from 0 to 24 h after VP-16 and CBDCA infusion was 1.91 and 113.6% of plasma, respectively. In two of the eight patients, the clinical response to treatment was a partial response and other patients showed no change. HODBBB and intraarterial combination chemotherapy with VP-16 and CBDCA may be useful in patients with brain tumors for maintenance chemotherapy.
- 社団法人日本薬学会の論文
- 1999-04-15
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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