Adriamycin-Lipiodol suspension for i. a. chemotherapy of hepatocellular carcinoma |
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Authors: | Yoshihiro Katagiri Kazuhide Mabuchi Tadanori Itakura Kohji Naora Kikuo Iwamoto Yoshimasa Nozu Shun-ichi Hirai Nobumasa Ikeda Toshio Kawai |
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Affiliation: | (1) Department of Pharmacy, Shimane Medical University Hospital, Enya-cho 89-1, 693 Izumo, Shimane, Japan;(2) Department of Pharmacy, Hirata Municipal Hospital, Nadabun-cho 613, 691 Hirata, Shimane, Japan;(3) Department of Surgery, Hirata Municipal Hospital, Nadabun-cho 613, 691 Hiratal, Shimane, Japan;(4) Department of Internal Medicine, Hirata Municipal Hospital, Nadabun-cho 613, 691 Hirata, Shimane, Japan |
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Abstract: | Summary Physicochemical properties of two types of adriamycin preparation, suspensions and emulsions prepared for i.a. chemotherapy of hepatocellular cacinoma, were investigated. A suspension was prepared by dispersing adriamycin directly into the lipid contrast medium, Lipiodol, whereas an emulsion was obtained by emulsifying an aqueous solution of adriamycin into Lipiodol. The dispersibility of the drug in each preparation was examined microscopically. The chemical stability of and drug release from the preparation were determined by high-performance liquid chromatography and spectrophotometry, respectively. The suspension was then given to ten patients with primary hepatocellular carcinoma. The suspension maintained good dispersibility without coagulation of drug particles, whereas coalescence of aqueous droplets and the resultant phase separation occurred 4 h after preparation of the emulsion. Both preparations maintained the initial drug content for at least 1 week at room temperature. The release of adriamycin was more prolonged in the suspension than in the emulsion. After i.a. administration of the suspension, a selective accumulation of Lipiodol in the tumor and decrease in serum -fetoprotein (AFP) levels were found in most patients. A significant amount of adriamycin was still detected in hepatic speciments resected from two patients 1 and 2 months after treatment. These findings suggest that the adriamycin-Lipiodol suspension may be a useful preparation for targeting chemotherapy to hepatocellular carcinoma. |
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