顺铂化疗患者皮肤中铂类药物药代动力学的无创随访

Noninvasive follow-up of platinum pharmacokinetics in the skin of patients on cisplatin chemotherapy.

作者信息

Gorodetsky R, Mou X, Vexler A, Kaufman B, Catane R, Loewenthal E

机构信息

Sharett Institute of Oncology, Hadassah University Hospital, Jerusalem, Isreal.

出版信息

Cancer. 1993 Jul 15;72(2):446-54. doi: 10.1002/1097-0142(19930715)72:2<446::aid-cncr2820720221>3.0.co;2-9.

DOI:10.1002/1097-0142(19930715)72:2<446::aid-cncr2820720221>3.0.co;2-9

PMID:8319176

Abstract

BACKGROUND

Treatment with high-dose cisdiammine-dichloroplatinum (II) (cisplatin, cDDP) often is associated with late complications, predominated by peripheral neuropathy. Pt deposition in different tissues may play a key role in the induction of many of these effects. Main topics of interest include the relationship between cDDP doses given during treatment and the long-term pharmacokinetics of the drug complexes in normal tissues and blood. Noninvasive examination of Pt in tissues during and after cDDP treatment are needed to clarify these points.

METHODS

A novel, high-sensitivity diagnostic x-ray spectrometry (DXS) method was used for the fast, noninvasive analysis of Pt in external tissues of patients with cancer treated with courses of cDDP. The Pt in a small skin area was excited by a monochromatic soft x-ray beam (14.6 KeV) and the spectral L lines emitted from the tissue were detected. A limit of detection below 1 microgram/g wet weight was reached. The pharmacokinetics of Pt in blood was investigated in parallel with the use of high-sensitivity, flameless atomic absorption spectrometry (AAS).

RESULTS

Follow-up of Pt concentrations in the skin of patients with cancer by DXS before cDDP treatment, during treatment, and up to 4 months after its completion, showed prolonged Pt deposition that corresponded to the net cumulative doses of the drug. Pt clearance from the skin fitted a monoexponential curve with a half-life of about 30 days. In comparison, the pharmacokinetics of total Pt in plasma showed a much faster, biexponential clearance with half-lives of 41 minutes and 5.2 days, respectively.

CONCLUSIONS

The amount of nonspecific Pt deposition in the tissues was found to depend on the total doses administered, the time interval between the courses, and the slow rate of clearance. Noninvasive measurements of tissue Pt levels may serve as a major tool in the evaluation of the induction of late cDDP complications.

摘要

背景

高剂量顺二氯二氨铂（II）（顺铂，cDDP）治疗常常与晚期并发症相关，主要是周围神经病变。铂在不同组织中的沉积可能在许多这些效应的诱导中起关键作用。主要关注的主题包括治疗期间给予的顺铂剂量与药物复合物在正常组织和血液中的长期药代动力学之间的关系。需要在顺铂治疗期间和之后对组织中的铂进行无创检查以阐明这些问题。

方法

一种新型的高灵敏度诊断X射线光谱法（DXS）用于对接受顺铂疗程治疗的癌症患者的外部组织中的铂进行快速、无创分析。通过单色软X射线束（14.6千电子伏特）激发小面积皮肤中的铂，并检测从组织发射的光谱L线。达到了低于1微克/克湿重的检测限。同时使用高灵敏度无火焰原子吸收光谱法（AAS）研究血液中铂的药代动力学。