Effect of sodium thiosulfate on cisplatin removal with complete hepatic venous isolation and extracorporeal charcoal hemoperfusion: A pharmacokineticevaluation

Background: Complete hepatic Venous isolation and extracorporeal charcoal h emoperfusion (HVI.CHP) can limit systemic exposure to high-dose chemotherap eutic agents when given by hepatic arterial infusion (HAI). The purpose of this study was to determine if the concomitant use of sodium thiosulfate (S TS) could further expand the advantages of pharmacologic delivery of HVI.CH P for cisplatin (CDDP) during HAI chemotherapy. Methods: CDDP (4mg/kg) was administered over 20 minutes via HAI under condi tions of HVI.CHP in 14 mongrel dogs. HVI.CHP was performed for 30 minutes a fter initiation of HAI. During CDDP infusion, 7 dogs each received 400 mg/k g STS (a 100-fold molar ratio to CDDP) over 20 minutes via the prefilter (S TS group) circuit line, while the remaining 7 dogs (controls)received no ST S. Blood samples were taken serially from the prefilter circuit line (hepat ic venous blood), postfilter line, and the left carotid artery (systemic bl ood). The free and total CDDP concentrations in these samples were determin ed by flameless atomic absorption spectrophotometry. Results: During 20 minutes HAI of CDDP, the mean CDDP extraction ratios (ER ) by CHP filter were always higher in the STS group than in the control gro up, regardless of the form (free or total) of CDDP. The differences between the STS and control groups in the extraction ratios of free and total CDDP were significant at all time points measured (P < .05). Consequently, syst emic exposure to CDDP, as assessed by area under the time-concentration cur ve of total CDDP, was significantly lower in the STS group than in the cont rol group (P < .05). Conclusions: These results indicated that concomitant STS infusion could fu rther increase the effect of HVI.CHP on CDDP removal after HAI.