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采用 ICP-MS 研究新型抗肿瘤超分子二环铂中铂的药代动力学、组织分布和血浆蛋白结合研究在大鼠和犬体内的情况。

Pharmacokinetics, tissue distribution, and plasma protein binding study of platinum originating from dicycloplatin, a novel antitumor supramolecule, in rats and dogs by ICP-MS.

机构信息

Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, Jiangsu, People's Republic of China.

出版信息

Biol Trace Elem Res. 2012 Aug;148(2):203-8. doi: 10.1007/s12011-012-9364-2. Epub 2012 Feb 28.

DOI:10.1007/s12011-012-9364-2
PMID:22367705
Abstract

Dicycloplatin, as a new antitumor supramolecule, was considered to have higher solubility and higher stability compared with carboplatin. The aim of the present study was to evaluate the pharmacokinetic characteristics of platinum originating from dicycloplatin. A rapid, sensitive, and specific method with inductively coupled plasma mass spectrometry (ICP-MS) has been developed for the determination of platinum in bio-samples. The study was performed in male rats and dogs at a single dose of 10 and 5 mg kg(-1) separately by intravenous injection. Pharmacokinetic parameters were calculated by non-compartmental method, and the dose of platinum was used in the calculation of these parameters. Results showed that plasma concentrations of platinum began to decrease rapidly initially but decline slowly with a long terminal phase. The mean half-life was 27.39 and 100.98 and clearance was 0.77 and 0.08 L/h/kg for rats and dogs separately. Tissue distribution showed that platinum originating from dicycloplatin had a certain distribution in testis and prostate. Plasma protein binding proportion of platinum was increased with time. In conclusion, this research investigated the pharmacokinetic characteristics including plasma kinetics, tissue distribution, and plasma protein binding of platinum originating from dicycloplatin in rats and dogs in detail for the first time by ICP-MS.

摘要

双环铂作为一种新型抗肿瘤超分子配合物,与顺铂相比,具有更高的溶解度和稳定性。本研究旨在评估双环铂中铂的药代动力学特征。采用电感耦合等离子体质谱法(ICP-MS)建立了一种快速、灵敏、特异的生物样品中铂的测定方法。该研究分别在雄性大鼠和犬中以 10 和 5mg/kg 的单剂量静脉注射进行。采用非房室模型法计算药代动力学参数,并在计算这些参数时使用铂的剂量。结果表明,铂的血浆浓度最初迅速下降,但随后缓慢下降,具有较长的末端相。大鼠和犬的平均半衰期分别为 27.39 和 100.98h,清除率分别为 0.77 和 0.08L/h/kg。组织分布显示,双环铂中的铂在睾丸和前列腺中有一定的分布。铂的血浆蛋白结合比例随时间增加而增加。总之,本研究首次通过 ICP-MS 详细研究了大鼠和犬中双环铂中铂的药代动力学特征,包括血浆动力学、组织分布和血浆蛋白结合。

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