Platinum in blood mononuclear cells from patients after cisplatin therapy

The feasibility of monitoring cisplatin chemotherapy by measuring platinum (Pt) concentrations in blood mononuclear cells was tested in six patients (four with squamous cell carcinomas of the head and neck, one with non-Hodgkin's lymphoma, and one with lung carcinoma). Blood samples (20 to 40 mL) were collected at intervals from 6 min to 21 days after an iv infusion of cisplatin (80 or 100 mg per m2). Blood mononuclear cells were harvested on a Ficoll-Hypaque gradient, washed repeatedly, counted, and homogenized by sonication in 0.5 mL of saline solution. Pt was analyzed in duplicate 40 microL samples of plasma (N = 26) or cell homogenates (N = 23) by electrothermal atomic absorption spectrophotometry with Zeeman background correction. Immediately after the cisplatin infusion, plasma Pt concentrations averaged 2.6 (SD +/- 0.2) mg per L and mononuclear cell Pt concentrations averaged 2.5 +/- 0.5 ng per 10(6) cells. At 24 to 26 hr post-infusion, plasma Pt concentrations averaged 1.6 +/- 0.2 mg per L and mononuclear cell Pt concentrations averaged 2.3 +/- 0.6 ng per 10(6) cells. Plasma Pt disappearance followed two-compartment kinetics in all patients; the plasma Pt disappearance half-time (T1/2, mean +/- SD) was 148 +/- 41 hours. The Pt concentrations in blood mononuclear cells diminished gradually during the period of observation; the T1/2 could not be reliably determined, but was estimated to be longer than two weeks. This study shows that Pt can be measured in mononuclear cells of patients after cisplatin treatment and that Pt disappears more slowly from blood mononuclear cells than from plasma of these patients.

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