Pharmacokinetics of cis-dichlorodiamine-platinum (II) in patients with oral cancer

Cisplatinum was administered by intra-venous injection and intra-arterial injection for the treatment of oral cancer patients. The protin-bound platinum levels and non-proteinbound platinum levels in plasma were measured. As results:(1) The non-protein-bound platinum level declined rapidly following the end of administration and cleared below the measurable level within 2 hours. The mean half-life time was 29.2 minutes in intra-arterial injection, and 31.9 minutes in intra-venous injection. Larger doses of cisplatin resulted in higher plasma levels of non-protein-bound platinum, which were not dose-dependent.(2) Total platinum level decreased in a biphasic mode with a mean α-phase half-life time of 57.5 minutes in intra-arterial injection and 51.6 minutes in intra-venous injection. But no significant difference was found in the changes of plasma concentration between intra-arterial and intravenous injection methods.(3) The maximum plasma concentration and area under the curve (AUC) of non-protein-bound platinum varied in proportion to the dose per area of body surface in intra-venous injection cases. In conclusion, it is considered that the optimal method of CDDP administration should be selected not only by the higher plasma concentration and wider AUC of non-protein-bound Pt but also by the decrease of side effects and the increase of antitumor effects.