1986 Volume 77 Issue 5 Pages 494-501
A new bioassay method for cis-diamminedichloroplatinum (CDDP) using a human tumor clonogenic assay (HTCA) was developed and used to examine the pharmacokinetics of the active form of CDDP in different schedules of administration. The inhibition of colony growth of tumor cells decreased with increase in the % of fetal calf serum in RPMI1640 containing CDDP. By means of this assay, four administration schedules (A, B, C and D) of CDDP were examined. In patients given 40mg/m2 of CDDP by iv infusion on day 1 twice with a 1hr interval (schedule A), total platinum was still detectable in plasma at 6hr by atomic absorption assay. However, the active form of CDDP was no longer detectable at 30min. In patients treated with 20mg/m2 of CDDP iv for 20min daily (schedule B) from day 1 to day 4, the level of total platinum showed a cumulative increase. However, the active form of CDDP was no longer detectable at 30min, and no cumulative effect was observed. In patients given a high dose (120mg/m2) of CDDP iv for 30min on day 1 (schedule C), the peak concentration of active form of CDDP was determined to be 5.0 to 7.0μg/ml, and a level of more than 1.0μg/ml was maintained even after 2hr in one case. In 2 patients of this group the concentrations of active form of CDDP determined by HTCA were the same as those of ultrafiltrable platinum detected by atomic absorption assay. In 2 of 3 patients given 100mg of CDDP into the pleural cavity, the active form of CDDP was detected in sera. High-dose CDDP administration was concluded to be preferable to low-dose therapy because of the higher peak concentration and longer residence time of the active form of CDDP in the plasma. Furthermore, it is suggested that a systemic effect of CDDP can be expected even when CDDP is given by intrapleural administration.
