[A method of cisplatin administration with the aid of high-dose bismuth subnitrate, and their pharmacokinetics]

Twelve Patients with malignant neoplasms were treated in twenty-five courses with high-dose Cisplatin and high-dose Bismuth Subnitrate. The pharmacokinetics of Bismuth Subnitrate and Cisplatin were studied in several courses. Bismuth Subnitrate was administered orally at a dose of 150 mg/kg/day for 10 days, and an average dose of 108 mg/m2 of cisplatin was administered intravenously on the 6th day after Bismuth Subnitrate administration. The concentration of Bismuth in blood and urine showed a similar increase, reaching a plateau 5 days after, and peaking 12 days after starting administration. It is estimated that 10-day administration of high-dose Bismuth Subnitrate was appropriate to maintain an adequate concentration of Bismuth for preinduction of Metallothionein in organs. The pharmacokinetics of cisplatin in plasma indicated as follows. a) In terms of the nephrotoxic factors, the Cmax of platinum did not increase dose-dependently, and total clearance of platinum was constant under the same time of injection; b) As for the antitumor effect, AUC of ultrafilterable (free) platinum increased dose-dependently. From the standpoint of pharmacology, high-dose Bismuth Subnitrate was believed to reduce the nephrotoxicity of cisplatin without reducing its antitumor effect.