Effect of sodium thiosulfate on cisplatin removal with complete hepatic venous isolation and extracorporeal charcoal hemoperfusion: a pharmacokinetic evaluation.
BACKGROUND
Complete hepatic venous isolation and extracorporeal charcoal hemoperfusion (HVI.CHP) can limit systemic exposure to high-dose chemotherapeutic agents when given by hepatic arterial infusion (HAI). The purpose of this study was to determine if the concomitant use of sodium thiosulfate (STS) could further expand the advantages of pharmacologic delivery of HVI.CHP for cisplatin (CDDP) during HAI chemotherapy.


METHODS
CDDP (4mg/kg) was administered over 20 minutes via HAI under conditions of HVI.CHP in 14 mongrel dogs. HVI.CHP was performed for 30 minutes after initiation of HAI. During CDDP infusion, 7 dogs each received 400 mg/kg STS (a 100-fold molar ratio to CDDP) over 20 minutes via the prefilter (STS group) circuit line, while the remaining 7 dogs (controls) received no STS. Blood samples were taken serially from the prefilter circuit line (hepatic venous blood), postfilter line, and the left carotid artery (systemic blood). The free and total CDDP concentrations in these samples were determined 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 group, 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, systemic exposure to CDDP, as assessed by area under the time-concentration curve of total CDDP, was significantly lower in the STS group than in the control group (P < .05).


CONCLUSIONS
These results indicated that concomitant STS infusion could further increase the effect of HVI.CHP on CDDP removal after HAI.
Kusunoki
N
N
First Department of Surgery, Kobe University, Faculty of Medicine, Japan.
Ku
Y
Y
Tominaga
M
M
Iwasaki
T
T
Fukumoto
T
T
Muramatsu
S
S
Sugimoto
T
T
Tsuchida
S
S
Takamatsu
M
M
Suzuki
Y
Y
Kuroda
Y
Y
D000818:Animals; D002606:Charcoal / Q000493:pharmacokinetics*; D002945:Cisplatin / Q000378:metabolism*; D004285:Dogs; D005112:Extracorporeal Circulation; D005260:Female; D006464:Hemoperfusion; D006503:Hepatic Veins / Q000378:metabolism*; D008297:Male; D013054:Spectrophotometry, Atomic; D013885:Thiosulfates / Q000493:pharmacokinetics*; D013997:Time Factors
D013885:Thiosulfates; D002606:Charcoal; C017717:sodium thiosulfate; D002945:Cisplatin