Determination of Optimal Dosage for Nedaplatin Based on Pharmacokinetic and Toxicodynamic Analysis

Abstract

Nedaplatin is a platinum derivative anticancer drug. To determine its target AUC in cancer patients, the relationship between platinum AUC and hematological toxicity after administration of nedaplatin was analyzed. The data for plasma unbound platinum concentration, platelet (PLT) and white blood cell (WBC) counts were retrospectively obtained from 108 courses administered to 74 Japanese adult cancer patients. PLT and WBC decreased significantly after nedaplatin administration. The results of linear regression analysis suggested that the relative reduction ratio of PLT significantly correlated with AUC after nedaplatin administration and the relationship was not affected by the dosing course of nedaplatin nor the combination of other cancer drugs. From these findings, it became possible to determine the target AUC based on the pre-dose value of PLT and the tolerable or target nadir of PLT after nedaplatin administration. By using a simple formula to predict the individual platinum clearance of nedaplatin from a patient's renal function, it is possible to determine the optimal dose for individuals by taking into consideration the adequate maximum tolerable AUC and individual platinum clearance.