[Pharmacokinetics of cis-dichlorodiammineplatinum (II)]

The pharmacokinetics of cis-dichlorodiammineplatinum (II) have been studied in 8 patients with advanced head and neck cancer. Plasma and urine platinum concentration were determined by atomic absorption spectrometry. Three different infusion methods were compared: 1) 24 hour continuous i.v. infusion; 2) 2 hour i. a. infusion and; 3) equally divided 5 daily i. a. infusion. In 4 patients receiving the 24 hour infusion, plasma platinum level had declined with second peak, which appeared 0.5-6 hours after end of infusion. Slow phase of half-life time of total platinum was very long ranged 86-197 hours. Non-protein bound platinum was rapidly cleared below the measurable level within 2 hours. At the end of 24 hour infusion, about 90% of plasma platinum was bound with plasma proteins. In a case of 2 hour infusion only one-half of platinum was bound. A patient receiving 2 hour infusion exhibited biphasic clearance of total platinum. In the 3 patients receiving divided daily infusion platinum concentration increased day by day. The level at 5th day was about 3 times higher than that of level at first day. In a patient with renal dysfunction slow phase half-life time prolonged markedly; however, his accumulative urinary excretion in first 24 hours did not diminish as compared with the patients with normal renal function.