文章基本信息

标题：Pharmacokinetics of Etoposide and Carboplatin in Cerebrospinal Fluid and Plasma during Hyperosmotic Disruption of the Blood Brain Barrier and Intraarterial Combination Chemotherapy
本地全文：下载
作者：Norifumi MORIKAWA ; Teruaki MORI ; Tatsuya ABE 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1999
卷号：22
期号：4
页码：428-431
DOI：10.1248/bpb.22.428
出版社：The Pharmaceutical Society of Japan
摘要：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/m² of VP-16 and 300 mg/m² 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.
关键词：etoposide;carboplatin;pharmacokinetics;cerebrospinal fluid;hyperosmotic disruption;intraarterial combination chemotherapy