Clinical kinetics of intact cisplatin and some related species

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Abstract
Human plasma concentrations of [the anticancer agent] cisplatin, total Pt and total filterable Pt were monitored in 24 patients after 50 or 100 mg/m2 of cisplatin by rapid i.v. injection. Half the patients at each dose were pretreated with mannitol. Total Pt levels declined in a triphasic fashion with a terminal half-life (t1/2) .gtoreq. 24 h. Both total filterable Pt and cisplatin levels declined in a monophasic manner and exhibited t1/2s of 0.3-0.5 h. The ratio of cisplatin to total filterable Pt in plasma remained constant (0.6-0.8) over the time period (2 h) during which they could be detected, while the ratio of the plasma levels of cisplatin to total Pt decreased continuously from .apprxeq.0.5 at 5 min to .apprx. 0.10 at 2 h. Larger doses of cisplatin caused higher plasma levels of all 3 spp. monitored, and although the increases appeared somewhat less than proportional to dose, terminal plasma slopes were not dose-dependent. Mannitol and the dose used did not affect the various species ratios. Mannitol did not affect plasma levels or terminal plasma decline.