Clinical kinetics of intact cisplatin and some related species

Abstract

Plasma concentrations of cisplatin, total platinum, and total filterable platinum were monitored in 24 patients after either 50 or 100 mg/m2 of cisplatin by rapid intravenous injection. Half the patients at each dose were pretreated with mannitol. Total platinum levels declined in a triphasic fashion with a terminal half-life (t1/2)greater than or equal to 24 hr. Both total filterable platinum and cisplatin levels declined in a monophasic manner and exhibited t1/2 of 0.3 to 0.5 hr. The ratio of cisplatin to total filterable platinum in plasma remained constant (0.6 to 0.8) over the time period (2 hr) during which they could be detected, while the ratio of the plasma levels of cisplatin to total platinum decreased continuously from approximately 0.5 at 5 min to approximately 0.10 at 2 hr. Larger doses of cisplatin resulted in higher plasma levels of all three species monitored, and although the increases appeared somewhat less than proportional to dose, terminal plasma slopes were not dose dependent. Neither mannitol nor dose had an effect on the various species ratios, nor did mannitol appear to affect either plasma levels or terminal plasma decline.

Phase I Pharmacokinetic and Pharmacodynamic Study of the Oral Protein Kinase C β-Inhibitor Enzastaurin in Combination with Gemcitabine and Cisplatin in Patients with Advanced Cancer

“…© 2007 American Association for Cancer clincancerres.aacrjournals.org Downloaded from and cisplatin (39), suggesting that enzastaurin does not influence either platinum elimination or gemcitabine pharmacokinetics.…”

Reinforcing Aerosol Cisplatin for Radiotherapy of Laryngeal Cancer.

“…m. (Himmelstein et al 1981). Then, we may well expect that those aliquots of CDDP would probably help killing the cells (Shimoyama 1973).…”

Novel bladder preservation therapy for locally invasive bladder cancer: Combined therapy using balloon-occluded arterial infusion of anticancer agent and hemodialysis with concurrent radiation

“…Cisplatin exerts its anti-tumor activity via the non-protein-bound form, which decreases rapidly after administration: its half-life is normally less than 60 min, decreasing to below the detection limit 4 h after administration (25,26). Accordingly, removal of non-proteinbound Pt immediately after administration of cisplatin, which markedly reduces systemic side effects, may be highly advantageous for patients undergoing selective intra-arterial infusion.…”