[Pharmacokinetic study of cisplatin and sodium thiosulfate in two-route-infusion chemotherapy]

In seven patients with head and neck cancer, two-route-infusion chemotherapy using cisplatin (CDDP) and sodium thiosulfate (STS) was performed and their pharmacokinetics were studied. As for the time of administration of STS, the treatment courses were classified into 4 groups: STS was given 10 minutes after the administration of CDDP in group I, 30 minutes in group II, 60 minutes in group III and the same schedule as group II in addition to prior loading of STS in group IV. The peak level of plasma CDDP was 1.27-3.33 micrograms/ml and the half-lives of the alpha-phase in groups I, II, III and IV were 58, 97, 126 and 44 minutes, respectively. The peak level of plasma non-protein-bound CDDP was 1.00 +/- 0.45 micrograms/ml and the half-life was 53 minutes. The peak level of plasma STS was 32.2 and 33.3 mg/dl and the half-life was 95 minutes. No serious side effect was observed but slight nausea and anorexia occurred in two courses. This study suggests that the liberation of CDDP from protein-bound CDDP was achieved by administration of STS and that the urinary excretion of CDDP from the plasma was also increased immediately after the administration of STS. The mechanism of relief of CDDP side effects by STS is supposed to involve both a neutralizing action CDDP and reversal of CDDP-induced, cross-linked DNA.