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借助高压氧合作用,抗癌药物卡铂在大鼠脑中的分布增加。

Increased distribution of carboplatin, an anti-cancer agent, to rat brains with the aid of hyperbaric oxygenation.

作者信息

Suzuki Y, Tanaka K, Neghishi D, Shimizu M, Murayama N, Hashimoto T, Yamazaki H

机构信息

Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Tokyo, Japan.

出版信息

Xenobiotica. 2008 Dec;38(12):1471-5. doi: 10.1080/00498250802478313.

DOI:10.1080/00498250802478313
PMID:18949658
Abstract
  1. The distribution of an anti-cancer agent carboplatin to brains was investigated in combination with hyperbaric oxygenation treatment in rats. 2. After intravenous administration of carboplatin (30 mg kg(-1)) to male Wistar rats, elimination curves of plasma drug concentrations plotted against a time of 45 min were not different with or without hyperbaric oxygenation (at 0.20-0.25 MPa for last 20 min) treatments. 3. Carboplatin concentrations of livers, lungs and kidneys in each group were similar at the endpoint of hyperbaric oxygenation treatment. 4. Under these atmosphere conditions (at 0.10 MPa), carboplatin concentration was at an undetectable level in rat brains (<0.1 microg g(-1) tissue, n = 6). On the contrary, carboplatin was detected in all brains tested at the levels of 0.5 +/- 0.3 microg g(-1) tissue (mean and standard deviation (SD), n = 6), 0.8 +/- 0.5 microg g(-1) tissue, and 0.4 +/- 0.2 microg g(-1) tissue in combination with hyperbaric oxygenation at 0.20, 0.22, and 0.25 MPa, respectively, at the endpoint of hyperbaric oxygenation treatment. 5. The results suggest that carboplatin could be uptaken into rat brains at the detectable levels by the aid of hyperbaric oxygenation, consistently with the reported findings of enhanced transendothelial permeability and improved clinical efficacy of carboplatin combined hyperbaric oxygenation therapy.
摘要
  1. 研究了抗癌药物卡铂在大鼠高压氧治疗联合应用时向脑内的分布情况。2. 给雄性Wistar大鼠静脉注射卡铂(30mg/kg)后,绘制45分钟内血浆药物浓度的消除曲线,无论有无高压氧治疗(最后20分钟为0.20 - 0.25MPa),曲线并无差异。3. 在高压氧治疗终点时,每组肝脏、肺和肾脏中的卡铂浓度相似。4. 在这些大气条件下(0.10MPa),大鼠脑内卡铂浓度处于检测不到的水平(<0.1μg/g组织,n = 6)。相反,在高压氧治疗终点时,分别在0.20、0.22和0.25MPa的高压氧联合治疗下,所有测试脑内均检测到卡铂,浓度分别为0.5±0.3μg/g组织(均值和标准差(SD),n = 6)、0.8±0.5μg/g组织和0.4±(此处原文可能有误,推测为0.4±0.2)μg/g组织。5. 结果表明,借助高压氧,卡铂能够以可检测到的水平进入大鼠脑内,这与报道的卡铂联合高压氧治疗时跨内皮通透性增强及临床疗效改善的研究结果一致。

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Increased distribution of carboplatin, an anti-cancer agent, to rat brains with the aid of hyperbaric oxygenation.借助高压氧合作用,抗癌药物卡铂在大鼠脑中的分布增加。
Xenobiotica. 2008 Dec;38(12):1471-5. doi: 10.1080/00498250802478313.
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