[Experimental studies on drug concentrations in the liver using intra-hepatic injection of anticancer drug in combination with temporary halting of abdominal blood flow].
In a case of CDDP of 5 mg/kg injection for 5 min via the hepatic artery of non-tumor bearing rat, we assessed the influence of concomitant aortic clamping for 5 min at the intraphrenic level, which resulted in a decrease in the portal blood flow. CDDP-Platinum concentrations in the liver of rats given CDDP injection plus aortic clamping were 20.7 +/- 1.6 micrograms/g, which was two times higher than that (10.1 +/- 1.7 micrograms/g) of rat given CDDP injection alone. This enhanced CDDP-platinum concentration remained 15, 30, and 60 min after injection, respectively 1.4, 1.4 and 2.1 times higher. On the other hand, CDDP-platinum concentrations in the kidney of rats given CDDP injection plus aortic clamping were 4.5 +/- 0.8 micrograms/g, only one tenth of that (49.7 +/- 3.4 micrograms/g) of rats given CDDP injection alone. At 15 and 30 min after injection, there was no significant difference in CDDP-platinum concentrations in the kidney between these two groups. Renal toxicity observed in the group given CDDP injection plus aortic clamping was significantly less than in the group given CDDP injection alone, while hepatic toxicity seen in the former group was the same as that in the latter one.
Nishioka
Y
Y
Second Dept. of Surgery, Tokyo Medical and Dental University.
Iwama
T
T
Ishida
H
H
Fukunari
H
H
Yamazaki
T
T
Okubo
Y
Y
Imajo
M
M
Mishima
Y
Y
Endo
S
S
D000818:Animals; D001012:Aorta, Abdominal / Q000473:pathology / Q000502:physiology; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003250:Constriction; D006499:Hepatic Artery; D007269:Injections, Intra-Arterial; D008099:Liver / Q000378:metabolism*; D011168:Portal System / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow
D002945:Cisplatin