Regional chemotherapy in the canine liver.
Using a fluorometric assay, mean drug levels of Adriamycin were significantly higher in the normal canine liver following bolus injection of this drug via the hepatic artery or portal vein as compared to hepatic tissue levels following systemic intravenous administration (P < 0.001). However, the variations in tissue levels observed after hepatic artery (+/- 16.8 mcg/gm tissue) or portal vein (+/- 21.1 mcg/gm) infusion were significantly wider than those observed after systemic (+/- 1.3 mcg/gm) administration (P = 0.03). Using C14-labeled drugs, regional infusion of Adriamycin through the hepatic artery or portal vein resulted in significantly higher mean drug levels in the liver than after systemic intravenous administration, but the difference was more pronounced with bolus infusion of the drug than 1-hour infusion. 5-FU bolus or 1-hour infusion in the hepatic artery resulted in significantly higher mean drug levels in the liver compared to peripheral intravenous administration, but this was not so with the 3-hour infusion. The above experiments confirm previous studies that regional chemotherapy results in higher drug levels in the regional tissues compared to systemic administration. They also: (1) demonstrate the spotty drug distribution in the regional tissues after regional administration, a potentially correctable problem, and (2) suggest that the advantage of intra-arterial infusion may be more pronounced within a certain range of infusion times.
Zografos
G C
GC
Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, New York.
Kanter
P
P
Sharma
S D
SD
Driscoll
D L
DL
Blumenson
L E
LE
Karakousis
C P
CP
D000818:Animals; D004285:Dogs; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005472:Fluorouracil / Q000008:administration & dosage / Q000493:pharmacokinetics; D006499:Hepatic Artery; D007262:Infusions, Intravenous; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism*; D011169:Portal Vein
D004317:Doxorubicin; D005472:Fluorouracil