[Pharmacokinetic evidence for the renal reabsorption of CDDP]

CDDP has had a wide use and a remarkable progress in cancer chemotherapy. Among others nephrotoxicity is the principal dose-limiting factor in this drug. So that the pharmacokinetics of CDDP mainly for the kidney was investigated in 4 patients with gynecological malignancies. CDDP was administered by short-term (about 45 minutes) intra-arterial infusion at a dose of 100 mg/body. Total CDDP (T) and non-protein-bound CDDP (NPB) concentrations in plasma declined in a biphasic manner, with a half life values of 0.506, 0.551 hr in alpha phase and 102, 96 hr in beta phase respectively. Protein-bound plasma CDDP (PB) in the time concentration curve showed two peaks, at the end of infusion and at about 3-5 hours after infusion to be followed by biphasic declining, which showed similarity to the simulation curve supposing the delayed influx. Total urinary excretion rate (up to 48 hours after infusion) was 15% on the average. It was shown that there was a close relation between urinary volume of less than 3 ml/min and NPB clearance (R = 0.877). And then there was a significant difference of NPB clearances by the kidney between cases of less than 200 ng/ml of NPB plasma concentration and those over 200 ng/ml. Binding proteins at the first and the second peak were analyzed by gel filtration method. At the second peak PB was mostly detected on the albumin fraction, which was different from the first peak. The mean estimated renal reabsorption of CDDP after 3 hours following injection was about 2 mg. (ABSTRACT TRUNCATED AT 250 WORDS)