N. Kusunoki et al., Effect of sodium thiosulfate on cisplatin removal with complete hepatic venous isolation and extracorporeal charcoal hemoperfusion: A pharmacokineticevaluation, ANN SURG O, 8(5), 2001, pp. 449-457
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.