[Alleviation of cisplatin toxicity by high-dose bismuth subnitrate and pharmacokinetics of bismuth subnitrate and cisplatin].

Abstract

Twelve patients with several malignant neoplasms, including lung and gastrointestinal carcinoma were treated with high-dose Cisplatin and high-dose Bismuth Subnitrate. Therapeutic efficacy and protective effect of high-dose Bismuth Subnitrate on toxicity of Cisplatin were evaluated in twenty-five courses of treatment. The Pharmacokinetics of Bismuth Subnitrate and Cisplatin were also studied in several courses. Bismuth Subnitrate was administered orally at a dose of 150 mg/kg/day for 10 days and a dose of 80-150 (Mean 108) mg/m2 of Cisplatin was administered intravenously on the day six of Bismuth Subnitrate administration. Toxicities of high-dose Cisplatin were minimal under administration of high-dose Bismuth Subnitrate and therapeutic efficacy was observed in several patients. The pharmacokinetics of Bismuth Subnitrate in plasma and urine demonstrated that 10 days administration of high-dose Bismuth Subnitrate was appropriate to maintain adequate concentration of Bismuth for preinduction of Metallothionein in organs. The pharmacokinetics of Cisplatin in plasma and urine demonstrated that deposition of total and ultrafilterable (free) platinum in blood were well described by a biphasic manner with a very rapid first phase and a very prolonged second phase, and that urine excretion of platinum was similar to the conventional manner. This study demonstrated that concurrent administration of high-dose Bismuth Subnitrate can permit the administration of high-dose Cisplatin with minimal toxicity and appropriate antitumor effect.