Antitumor activity of cis-diamminedichloroplatinum (II) depends on its time × concentration product against human gastric cancer cell lines in vitro

A pharmacodynamic study of cisplatin (DDP) was conducted using the gastric cancer cell lines MKN-45 and MKN-74 in vitro. Ten thousand tumor cells were incubated with 0.4–500 μg/ml DDP for 1–25 h, followed by recovery culture for a further 48 h. At the end of incubation, cell viability was detected by the MTT end-point, and the inhibition rate was compared in relation to the incubation time, DDP concentration, and the time × concentration product (area under the curve in vitro: AUC vitro). In both of the cell lines, the IC50 and IC90 values decreased as the exposure time increased, going a linear curve with a slope of almost — 1, and showing a typical log-log AUC vitro-dependent curve. These results indicate that the antitumor activity of DDP is dependent on its AUC vitro, suggesting the clinical usefulness of this drug when administered daily in small divided doses. © 1995 Wiley-Liss, Inc.