Determination of the in vivo pharmacokinetics of palladium-bacteriopheophorbide (WST09) in EMT6 tumour-bearing Balb/c mice using graphite furnace atomic absorption spectroscopy
Determination of the in vivo pharmacokinetics of palladium-bacteriopheophorbide (WST09) in EMT6 tumour-bearing Balb/c mice using graphite furnace atomic absorption spectroscopy
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DOI：
10.1039/b403534h
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发表时间：
2004-01-01
影响因子：
3.1
通讯作者：
Pottier, RH
中科院分区：
文献类型：
--
作者：
Brun, PH;DeGroot, JL;Pottier, RH
钯-细菌脱镁叶绿酸（WST 09），一种新的细菌叶绿素衍生物，目前正在研究用作光动力治疗（PDT）药物，由于其在近红外区域的强吸收和其在照射时有效产生单线态氧的能力。在这项研究中，我们确定了WST 09在雌性EMT 6荷瘤Balb/c小鼠中的药代动力学和组织分布，以确定该药物是否在肿瘤组织中发生选择性蓄积。总共41只小鼠通过尾静脉推注给予WST 09，剂量水平为5.0 +/- 0.8 mg/kg（-1）。在注射后0.08、0.25、0.5、1.0、3.0、6.0、9.0、12、24、48、72和96小时各处死3至6只小鼠，并处死另外3只未施用WST 09的对照小鼠。从每只小鼠获得终末血样以及肝脏、皮肤、肌肉、肾脏和肿瘤样品，并使用石墨炉原子吸收光谱法（GFAAS）分析钯含量（来自WST 09）。然后计算血浆和组织中WST 09的代表性浓度。在血浆、肾脏和肝脏中观察到双相动力学，从这些组织中的每种组织中清除相对较快。在研究的所有时间点，皮肤、肌肉和肿瘤均未显示任何显著蓄积。相对于血浆，在肿瘤和正常组织中未观察到选择性药物蓄积。因此，本研究的结果表明，与WST 09在肿瘤组织中的选择性积累相反，WST 09在循环中产生的血管靶向作用可能是在其他WST 09研究中观察到的肿瘤中PDT效应的原因。
Palladium-bacteriopheophorbide (WST09), a novel bacteriochlorophyll derivative, is currently being investigated for use as a photodynamic therapy (PDT) drug due to its strong absorption in the near-infrared region and its ability to efficiently generate singlet oxygen when irradiated. In this study, we determined the pharmacokinetics and tissue distribution of WST09 in female EMT6 tumour-bearing Balb/c mice in order to determine if selective accumulation of this drug occurs in tumour tissue. A total of 41 mice were administered WST09 by bolus injection into the tail vein at a dose level of 5.0 +/- 0.8 mg kg(-1). Three to six mice were sacrificed at each of 0.08, 0.25, 0.5, 1.0, 3.0, 6.0, 9.0, 12, 24, 48, 72, and 96 h post injection, and an additional three control mice were sacrificed without having been administered WST09. Terminal blood samples as well as liver, skin, muscle, kidney and tumour samples were obtained from each mouse and analyzed for palladium content (from WST09) using graphite furnace atomic absorption spectroscopy (GFAAS). The representative concentration of WST09 in the plasma and tissues was then calculated. Biphasic kinetics were observed in the plasma, kidney, and liver with clearance from each of these tissues being relatively rapid. Skin, muscle and tumour did not show any significant accumulation at all time points investigated. No selective drug accumulation was seen in the tumour and normal tissues, relative to plasma. Thus the results of this study indicate that vascular targeting resulting from WST09 in the circulation, as opposed to selective WST09 accumulation in tumour tissues, may be responsible for PDT effects in tumours that have been observed in other WST09 studies.