NONINVASIVE FOLLOW-UP OF PLATINUM PHARMACOKINETICS IN THE SKIN OF PATIENTS ON CISPLATIN CHEMOTHERAPY

Background. Treatment with high-dose cisdiammine-dichloroplatinum (II) (cisplatin, cDDP) often is associated with late complications, predom inated by peripheral neuropathy. Pt deposition in different tissues ma y play a key role in the induction of many of these effects. Main topi cs of interest include the relationship between cDDP doses given durin g treatment and the long-term pharmacokinetics of the drug complexes i n normal tissues and blood. Noninvasive examination of Pt in tissues d uring and after cDDP treatment are needed to clarify these points. Met hods. A novel, high-sensitivity diagnostic x-ray spectrometry (DXS) me thod was used for the fast, noninvasive analysis of Pt in external tis sues 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 mug/g wet weight was reached. The pharmaco kinetics of Pt in blood was investigated in parallel with the use of h igh-sensitivity, flameless atomic absorption spectrometry (AAS). Resul ts. Follow-up of Pt concentrations in the skin of patients with cancer by DXS before cDDP treatment, during treatment, and up to 4 months af ter its completion, showed prolonged Pt deposition that corresponded t o the net cumulative doses of the drug. Pt clearance from the skin fit ted a monoexponential curve with a half-life of about 30 days. In comp arison, the pharmacokinetics of total Pt in plasma showed a much faste r, 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. Non invasive measurements of tissue Pt levels may serve as a major tool in the evaluation of the induction of late cDDP complications.