Pharmacokinetic study for combination therapy of cisplatin and peplomycin.

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Both Cisplatin (CDDP) and Peplomycin (PEP) are effective for head and neck cancer, and the combined therapy of the two drugs exerts effective syner-gistic effects. In the present study, the mechanism of the synergism was examined from a pharmacokinetic aspect. First, the pharmacokinetics of CDDP was studied. CDDP was transformed into protein-bound CDDP in the blood. The half life of CDDP in the alpha phase (up to 2 hours after administration) was 0.99 hour; in the beta phase (up to 150.65 hours after administration) it was 150.65 hours. CDDP was proved to persist in the blood in the form of protein-bound CDDP. The in vitro study revealed that the anti-tumor activity of CDDP against the HeLa cells in plasma decreased with time. This indicated that only non-protein-bound CDDP had an anti-tumor effect. Based upon the above findings, we performed an in vitro experiment to determine if PEP could have some promoting effect on the release of non-protein-bound CDDP, which has anti-tumor activity, from protein-bound CDDP. No such effect was observed. The binding between CDDP and plasma protein appeared to be irreversible, and a mechanism that concurrently used PEP may release non-protein-bound CDDP from protein-bound CDDP was denied.