Disposition of total and free cisplatin on two consecutive treatment cycles in patients with ovarian cancer.

The disposition of total and ultrafilterable cisplatin was determined in 12 women with ovarian carcinoma receiving cyclophosphamide 500 mg/m2, adriamycin 50 mg/m2 and cisplatin 50 mg/m2 during their first and second course. Plasma samples were obtained over 96 h following the completion of the cisplatin infusion and assayed for total platinum by atomic absorption spectroscopy. Plasma samples obtained up to 4 h after cisplatin infusion contained measurable ultrafilterable (free) cisplatin. The mean disposition of free cisplatin conformed to a two-compartment model with a mean terminal half-life (+/- SD) of 46.2 +/- 20.2 min during the first course and 37.8 +/- 18.0 min during the second course of therapy. The mean disposition of total cisplatin conformed to a three-compartment model with a mean terminal half-life (+/- SD) of 57.8 +/- 19.3 h during the first course and 86.6 +/- 33.3 h during the second course of therapy. We found that the mean total cisplatin levels were significantly higher during the second course than the first course and the total body clearance of total platinum decreased from the first to the second course. Divided urine collections were obtained over 24 h after completion of cisplatin infusion, but cisplatin was not always detectable at all time intervals. The total fraction recovered was 0.14 and 0.12 of administered dose after the first and the second course, respectively. Renal clearance was 0.61 +/- 0.32 l/h/m2 and 0.45 +/- 0.16 l/h/m2 for the first and the second course, respectively. We conclude that: urinary platinum excretion is variable between patients and with time; a trend to decreased renal clearance of platinum from first to second course may be due to a decrease in renal excretion of cisplatin; and the body's elimination pathways clear less platinum upon repeat administration.