[Comparison of hepatic tissue extraction rates of cytotoxic anticancer drugs during hepatic arterial chemotherapy--evaluation using direct hemoperfusion under hepatic venous isolation].
Hepatic extraction rates (ER) of anticancer drugs during hepatic arterial infusion were investigated with the aid of direct hemoperfusion (DHP) under hepatic venous isolation (HVI). Using mongrel dogs (n = 6), adriamycin (ADR), mitomycin C (MMC) and cisplatin (CDDP) were simultaneously administered to the hepatic artery at each dosage of 1 mg/kg in 10 minutes under HVI.DHP. Hepatic venous flow and plasma concentrations of each drug at the carotid artery, the inlet and outlet sides of DHP were periodically determined during HVI.DHP. Based on these data, drug adsorption and removal rates were estimated. In addition, hepatic tissue uptakes of each drug were calculated from the amounts of drug administered and leaked in the hepatic effluent. Subsequently, the percentage of tissue uptake of each drug to the amount of drug administered was determined as ER of each drug. Drug adsorption rates during the first 10 minutes after infusion showed no significant difference among three drugs. Drug removal rate of CDDP tended to be higher than those of other two drugs. ER of CDDP (54.8 +/- 18.3%) were significantly lower (p < 0.01) as compared to ADR (84.4 +/- 16.2%) and MMC (83.1 +/- 15.7%). These results indicate that ER of each drug should be taken into consideration to determine appropriate drug for hepatic arterial chemotherapy.
Ku
Y
Y
First Department of Surgery, Kobe University School of Medicine.
Samizo
M
M
Fukumoto
T
T
Shiki
H
H
Maekawa
Y
Y
Iwasaki
T
T
Tominaga
M
M
Kuroda
Y
Y
Saitoh
Y
Y
D000327:Adsorption; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics; D004285:Dogs; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics; D006464:Hemoperfusion / Q000379:methods*; D006499:Hepatic Artery; D006503:Hepatic Veins; D007261:Infusions, Intra-Arterial; D008099:Liver / Q000378:metabolism*; D008937:Mitomycins / Q000008:administration & dosage / Q000493:pharmacokinetics
D008937:Mitomycins; D004317:Doxorubicin; D002945:Cisplatin